{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:59:44Z","timestamp":1791824384729,"version":"4.3.4"},"reference-count":189,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Diketopiperazines (DKPs) are biologically important cyclic dipeptides widespread in nature, associated primarily with microorganisms. This is the case for the 2,5-DKP derivative cyclo(L-Leu-L-Pro) (cLP), also known as gancidin W or PPDHMP, identified from a variety of bacteria and fungi, and occasionally found in food products. The present review retraces the discovery of cLP, its identification in living species, its chemical syntheses, and its biochemical properties. In bacteria, cLP is often associated with other DKPs to serve as a defense element against other microorganisms and\/or as a regulator of bacterial growth. cLP plays a role in quorum-sensing and functions as an anticariogenic and antifungal agent. The antimicrobial mechanism of action and molecular targets of cLP are evoked. The interest in cLP for combatting certain parasitic diseases, such as malaria, and cancers is discussed. The capacity of cLP to interact with CD151 and to down-regulate the expression of this tetraspanin can be exploited to reduce tumor dissemination and metastases. The review sheds light on the pharmacology and specific properties of cyclo(L-Leu-L-Pro), which can be useful for the development of a novel therapeutic approach for different human pathologies. It is also of interest to help define the bioactivity and mechanisms of action of closely related DKP-based natural products.<\/jats:p>","DOI":"10.3390\/md23100397","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:31Z","timestamp":1760028871000},"page":"397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Insights into the Bioactivities and Mechanism of Action of the Microbial Diketopiperazine Cyclic Dipeptide Cyclo(L-leucyl-L-prolyl)"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-9357","authenticated-orcid":false,"given":"Christian","family":"Bailly","sequence":"first","affiliation":[{"name":"UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, CNRS, Inserm, OncoLille Institute, University of Lille, 59000 Lille, France"},{"name":"Institute of Pharmaceutical Chemistry Albert Lespagnol (ICPAL), Faculty of Pharmacy, University of Lille, 59006 Lille, France"},{"name":"OncoWitan, 59290 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s00044-022-03003-9","article-title":"Espinosa-Bustos C.2,3-Diketopiperazine as potential scaffold to develop new anti-Chagasic agents","volume":"32","author":"Salas","year":"2023","journal-title":"Med. Chem. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Du, R.R., Wang, R.Y., Zhou, J.C., Gao, H.H., Qin, W.J., Duan, X.M., Yang, Y.N., Zhang, X.W., and Zhang, P.C. (2024). Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis. Bioorganic Chem., 151.","DOI":"10.1016\/j.bioorg.2024.107618"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, Y., Liu, T., Pan, G., Li, Y., Ma, G., Hou, Y., Zhu, N., and Xu, X. (2025). Orychophragvioline A, a Novel Alkaloid Isolated from Orychophragmus violaceus with Anti-Cervical Cancer Activity. Molecules, 30.","DOI":"10.3390\/molecules30081759"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1016\/j.ejmech.2011.07.027","article-title":"Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 1: Perhydropyrrole[1,2-a]pyrazines","volume":"46","author":"Dawidowski","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ejmech.2011.11.032","article-title":"Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 2: Perhydropyrido[1,2-a]pyrazines","volume":"48","author":"Dawidowski","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1007\/s00044-013-0800-4","article-title":"Multicomponent synthesis and anticonvulsant activity of monocyclic 2,6-diketopiperazine derivatives","volume":"23","author":"Dawidowski","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.4155\/fmc-2018-0599","article-title":"Novel 2,6-diketopiperazine-derived acetohydroxamic acids as promising anti-Trypanosoma brucei agents","volume":"11","author":"Fytas","year":"2019","journal-title":"Future Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1021\/acsmedchemlett.4c00111","article-title":"New Lipophilic Hydroxamates as Promising Trypanocidal Agents: Design, Synthesis, SAR, and Conformational Behavior Studies","volume":"15","author":"Fytas","year":"2024","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Garrido Gonz\u00e1lez, F.P., Mac\u00edas P\u00e9rez, M.E., Rodr\u00edguez Cort\u00e9s, O., Mera Jim\u00e9nez, E., and Mancilla Percino, T. (2025). Selective Antiproliferative and Apoptotic Effects of 2,6-Diketopiperazines on MDA-MB-231 Triple-Negative Breast Cancer. Chem. Biol. Drug Des., 105.","DOI":"10.1111\/cbdd.70098"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1021\/acs.jnatprod.4c00478","article-title":"Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways","volume":"87","author":"Khong","year":"2024","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/bs.alkal.2023.06.002","article-title":"Total synthesis of complex 2,5-diketopiperazine alkaloids","volume":"90","author":"Walker","year":"2023","journal-title":"Alkaloids Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1007\/s11030-024-10835-7","article-title":"Design, synthesis, and structure-activity relationship study of novel plinabulin derivatives as anti-tumor agents based on the co-crystal structure","volume":"29","author":"Wang","year":"2025","journal-title":"Mol. Divers."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S2213-2600(24)00178-4","article-title":"Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): A phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial","volume":"12","author":"Han","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bi, S., Cao, Y., Fang, S., Chu, Y., Zhang, Z., Li, M., Yu, R., Yang, J., Tang, Y., and Qiu, P. (2025). The Novel Diketopiperazine Derivative, Compound 5-3, Selectively Inhibited the Proliferation of FLT3-ITD Mutant Acute Myeloid Leukemia (AML) Cells. Mar. Drugs, 23.","DOI":"10.3390\/md23070289"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"597","DOI":"10.2174\/0113816128291798240201112916","article-title":"2,5-Diketopiperazines (DKPs): Promising Scaffolds for Anticancer Agents","volume":"30","author":"Goher","year":"2024","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1021\/cr200398y","article-title":"2,5-Diketopiperazines: Synthesis, reactions, medicinal chemistry, and bioactive natural products","volume":"112","author":"Borthwick","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1007\/s00253-021-11178-1","article-title":"Modifications of diketopiperazines assembled by cyclodipeptide synthases with cytochrome P(450) enzymes","volume":"105","author":"Harken","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, X., Li, Y., Zhang, X., Lai, D., and Zhou, L. (2017). Structural Diversity and Biological Activities of the Cyclodipeptides from Fungi. Molecules, 22.","DOI":"10.3390\/molecules22122026"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Turkez, H., Cacciatore, I., Arslan, M.E., Fornasari, E., Marinelli, L., Di Stefano, A., and Mardinoglu, A. (2020). Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates. Biomolecules, 10.","DOI":"10.3390\/biom10050737"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.peptides.2013.09.019","article-title":"Purification, structural elucidation and bioactivity of tryptophan containing diketopiperazines, from Comamonas testosteroni associated with a rhabditid entomopathogenic nematode against major human-pathogenic bacteria","volume":"53","author":"Kumar","year":"2014","journal-title":"Peptides"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mosetti, V., Rosetti, B., Pierri, G., Bellotto, O., Adorinni, S., Bandiera, A., Adami, G., Tedesco, C., Crosera, M., and Magnano, G.C. (2022). Cyclodipeptides: From Their Green Synthesis to Anti-Age Activity. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102342"},{"key":"ref_22","first-page":"97","article-title":"Gancidin, An Antitumor Substance Derived from Streptomyces sp. I","volume":"9","author":"Aiso","year":"1956","journal-title":"J. Antibiot. Ser. A"},{"key":"ref_23","first-page":"150","article-title":"Purification and Isolation Study on Gancidins","volume":"11","author":"Wakaki","year":"1958","journal-title":"J. Antibiot. Ser. A"},{"key":"ref_24","first-page":"535","article-title":"Studies on an antitumor substance, gancidin. Mycological study on the strain AAK-84 and production, purification of active fractions","volume":"33","author":"Suzuki","year":"1957","journal-title":"J. Chiba Med. Soc."},{"key":"ref_25","first-page":"528","article-title":"Studies on Antibacterial Activity of Gancidin (Rept. 2.)","volume":"33","author":"Suzuki","year":"1957","journal-title":"J. Chiba Med. Soc."},{"key":"ref_26","first-page":"169","article-title":"A rapid agar dilution technique for the estimation of antitumor-cell activity","volume":"9","author":"Arai","year":"1956","journal-title":"J. Antibiot. Ser. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1021\/ja01150a516","article-title":"Isolation of L-leucyl-Lproline anhydride from microbiological fermentations","volume":"3","author":"Johnson","year":"1951","journal-title":"J. Am. Chem. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1248\/cpb.10.154","article-title":"L-Leucyl-L-Proline from peptone","volume":"10","author":"Kosuge","year":"1962","journal-title":"Chem. Pharm. Bull."},{"key":"ref_29","first-page":"530","article-title":"Isolation of l-Leucyl-l-Proline Anhydride from the Culture Filtrate of Streptomyces sp. S-580","volume":"24","author":"Koaze","year":"1960","journal-title":"J. Agric. Chem. Soc. Japan"},{"key":"ref_30","first-page":"393","article-title":"A review of hypotheses of the structure of proteins","volume":"8","author":"Vickery","year":"1928","journal-title":"Phys. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1248\/cpb.10.152","article-title":"Isolation and Properties of Helmintin (C11H18N2O2), an Antifungal Substance produced by Helminthosporium siccans","volume":"10","author":"Inagaki","year":"1962","journal-title":"Chem. Pharm. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3987\/S-1977-01-0341","article-title":"Isolation and Structure Elucidation of Gancidin W","volume":"7","author":"Jain","year":"1977","journal-title":"Heterocycles"},{"key":"ref_33","first-page":"140","article-title":"Corollospora pulchella, a marine fungus producing antibiotics, melinacidins III, IV and gancidin W","volume":"37","author":"Furuya","year":"1985","journal-title":"Annu. Rep. Sankyo Res. Lab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/prac.19983400702","article-title":"Advances in chemical studies on low-molecular weight metabolites of marine fungi","volume":"340","author":"Biabani","year":"1998","journal-title":"J. Prakt. Chem.\/Chem.-Ztg."},{"key":"ref_35","first-page":"164","article-title":"Marine Streptomyces paradoxus VITALK03 derived gancidin W mediated cytotoxicity through Ras-Raf-MEK-ERK signalling pathway","volume":"16","author":"Ravi","year":"2017","journal-title":"Indian J. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/1874847301705010031","article-title":"Antidiabetic and Antioxidant Potential of GancidinW from VITALK03","volume":"5","author":"Ravi","year":"2017","journal-title":"Open Bioact. Compd. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2323\/jgam.48.321","article-title":"Isolation and characterization of Streptomyces sp. KH-614 producing anti-VRE (vancomycin-resistant enterococci) antibiotics","volume":"48","author":"Rhee","year":"2002","journal-title":"J. Gen. Appl. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s12275-015-5076-6","article-title":"In vivo antimalarial activity of the endophytic actinobacteria, Streptomyces SUK 10","volume":"53","author":"Baba","year":"2015","journal-title":"J. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2147\/DDDT.S121283","article-title":"Gancidin W, a potential low-toxicity antimalarial agent isolated from an endophytic Streptomyces SUK10","volume":"11","author":"Zin","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_40","first-page":"504","article-title":"Bioactivity-Guided Extraction and Identification of Antibacterial Compound from Marine Actinomycetes Strains Isolated from Costal Soil Samples of Rameswaram and Dhanushkodi, Tamil Nadu, India","volume":"10","author":"Ravi","year":"2016","journal-title":"Asian J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.4172\/pharmaceutical-sciences.1000460","article-title":"Extraction and Identification of Gancidin W from Marine Streptomyces sp. VITLGK012","volume":"80","author":"Ravi","year":"2018","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Khan, M.S., Gao, J., Munir, I., Zhang, M., Liu, Y., Moe, T.S., Xue, J., and Zhang, X. (2021). Characterization of Endophytic Fungi, Acremonium sp., from Lilium davidii and Analysis of Its Antifungal and Plant Growth-Promoting Effects. Biomed. Res. Int., 2021.","DOI":"10.1155\/2021\/9930210"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ejar.2016.03.001","article-title":"Chemical characterization & bioactivity of diketopiperazine derivatives from the mangrove derived Pseudonocardia endophytica","volume":"42","author":"Mangamuri","year":"2016","journal-title":"Egypt. J. Aquat. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jamal, Q., Cho, J.Y., Moon, J.H., Munir, S., Anees, M., and Kim, K.Y. (2017). Identification for the First Time of Cyclo(d-Pro-l-Leu) Produced by Bacillus amyloliquefaciens Y1 as a Nematocide for Control of Meloidogyne incognita. Molecules, 22.","DOI":"10.3390\/molecules22111839"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gowrishankar, S., Sivaranjani, M., Kamaladevi, A., Ravi, A.V., Balamurugan, K., and Karutha Pandian, S. (2016). Cyclic dipeptide cyclo(l-leucyl-l-prolyl) from marine Bacillus amyloliquefaciens mitigates biofilm formation and virulence in Listeria monocytogenes. Pathog. Dis., 74.","DOI":"10.1093\/femspd\/ftw017"},{"key":"ref_46","first-page":"874","article-title":"Studies on constituents of cultures of fungus Phellinus igniarius","volume":"36","author":"Wu","year":"2011","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mangrolia, U., and Osborne, W.J. (2020). Staphylococcus xylosus VITURAJ10: Pyrrolo [1,2alpha] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) (PPDHMP) producing, potential probiotic strain with antibacterial and anticancer activity. Microb. Pathog., 147.","DOI":"10.1016\/j.micpath.2020.104259"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.21608\/ejchem.2024.325664.10571","article-title":"Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl), as the primary secondary metabolite of Bacillus spp., could be an effective antifungal agent against the soil-borne fungus, Sclerotium bataticola","volume":"67","author":"Abdelkhalek","year":"2024","journal-title":"Egypt. J. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Manam, M., Srivatsa, S., and Osborne, W.J. (2025). Endophytic bacteria of Gracilaria edulis in combating human bacterial pathogens by PPDHMP\u2014A crude to single molecule product development approach. Microb. Pathog., 202.","DOI":"10.1016\/j.micpath.2025.107431"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Buragohain, T., Dey, P., and Osborne, W.J. (2023). In vitro studies on the inhibition of microbial pathogens by PPDHMP synthesized by Bacillus sp.; an endophyte of Citrus limon (Kaji nemu). Food Biosci., 55.","DOI":"10.1016\/j.fbio.2023.103003"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Prasad, J.K., Pandey, P., Anand, R., and Raghuwanshi, R. (2021). Drought Exposed Burkholderia seminalis JRBHU6 Exhibits Antimicrobial Potential Through Pyrazine-1,4-Dione Derivatives Targeting Multiple Bacterial and Fungal Proteins. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.633036"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s10495-016-1221-x","article-title":"Anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP) extracted from a new marine bacterium, Staphylococcus sp. strain MB30","volume":"21","author":"Lalitha","year":"2016","journal-title":"Apoptosis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.micpath.2018.03.011","article-title":"Antibiofilm effect of Nocardiopsis sp. GRG 1 (KT235640) compound against biofilm forming Gram negative bacteria on UTIs","volume":"118","author":"Rajivgandhi","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s12275-013-3521-y","article-title":"Cyclic dipeptides from lactic acid bacteria inhibit proliferation of the influenza A virus","volume":"51","author":"Kwak","year":"2013","journal-title":"J. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s12275-014-3520-7","article-title":"Cyclic dipeptides from lactic acid bacteria inhibit the proliferation of pathogenic fungi","volume":"52","author":"Kwak","year":"2014","journal-title":"J. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Son, J., Hong, Y., Seong, H., Oh, Y.S., and Kwak, M.K. (2024). The high-throughput solid-phase extraction of cis-cyclo(L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro) from Lactobacillus plantarum demonstrates efficacy against multidrug-resistant bacteria and influenza A (H3N2) virus. Front. Mol. Biosci., 11, Erratum in Front. Mol. Biosci. 2025, 12, 1605848.","DOI":"10.3389\/fmolb.2025.1605848"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kim, J., Kim, J.C., and Sang, M.K. (2023). Identification of isomeric cyclo(leu-pro) produced by Pseudomonas sesami BC42 and its differential antifungal activities against Colletotrichum orbiculare. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1230345"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Saadouli, I., Zendah El Euch, I., Trabelsi, E., Mosbah, A., Redissi, A., Ferjani, R., Fhoula, I., Cherif, A., Sabatier, J.M., and Sewald, N. (2020). Isolation, Characterization and Chemical Synthesis of Large Spectrum Antimicrobial Cyclic Dipeptide (l-leu-l-pro) from Streptomyces misionensis V16R3Y1 Bacteria Extracts. A Novel 1H NMR Metabolomic Approach. Antibiotics, 9.","DOI":"10.3390\/antibiotics9050270"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Salman, M., Tariq, A., Mustafa, G., Javed, M.R., Naheed, S., and Qamar, S.A. (2022). Cyclo(L-Leucyl-L-Prolyl) from Lactobacillus coryniformis BCH-4 inhibits the proliferation of Aspergillus flavus: An in vitro to in silico approach. Arch. Microbiol., 204.","DOI":"10.1007\/s00203-022-02884-z"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ivanov, I., Petrov, K., Lozanov, V., Hristov, I., Wu, Z.J., Liu, Z.M., and Petrova, P. (2021). Bioactive Compounds Produced by the Accompanying Microflora in Bulgarian Yoghurt. Processes, 9.","DOI":"10.3390\/pr9010114"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liu, R., Kim, A.H., Kwak, M.K., and Kang, S.O. (2017). Proline-Based Cyclic Dipeptides from Korean Fermented Vegetable Kimchi and from Leuconostoc mesenteroides LBP-K06 Have Activities against Multidrug-Resistant Bacteria. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00761"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7466","DOI":"10.1128\/AEM.70.12.7466-7473.2004","article-title":"Cyclo(L-leucyl-L-prolyl) produced by Achromobacter xylosoxidans inhibits aflatoxin production by Aspergillus parasiticus","volume":"70","author":"Yan","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1080\/14786419.2019.1677652","article-title":"A new diketopiperazine from an endophytic fungus Aspergillus aculeatus F027","volume":"35","author":"Ma","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.resmic.2014.03.004","article-title":"Inhibitory efficacy of cyclo(L-leucyl-L-prolyl) from mangrove rhizosphere bacterium-Bacillus amyloliquefaciens (MMS-50) toward cariogenic properties of Streptococcus mutans","volume":"165","author":"Gowrishankar","year":"2014","journal-title":"Res. Microbiol."},{"key":"ref_65","first-page":"74","article-title":"Production of Anti-Inflammatory Pyrrol Compound from Marine Bacillus baekryungensis AMHSU","volume":"8","author":"Abouelwafa","year":"2016","journal-title":"World J. Fish. Marine Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"11146","DOI":"10.3390\/molecules170911146","article-title":"Antitrypanosomal alkaloids from the marine bacterium Bacillus pumilus","volume":"17","author":"Spadafora","year":"2012","journal-title":"Molecules"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/j.1365-2672.2012.05385.x","article-title":"Identification of antimicrobial compound, diketopiperazines, from a Bacillus sp. N strain associated with a rhabditid entomopathogenic nematode against major plant pathogenic fungi","volume":"113","author":"Mohandas","year":"2012","journal-title":"J. Appl. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"402","DOI":"10.5423\/PPJ.OA.11.2016.0255","article-title":"Cyclic Dipeptides from Bacillus vallismortis BS07 Require Key Components of Plant Immunity to Induce Disease Resistance in Arabidopsis against Pseudomonas Infection","volume":"33","author":"Noh","year":"2017","journal-title":"Plant Pathol. J."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ren, Z., Xie, L., Okyere, S.K., Wen, J., Ran, Y., Nong, X., and Hu, Y. (2022). Antibacterial Activity of Two Metabolites Isolated From Endophytic Bacteria Bacillus velezensis Ea73 in Ageratina adenophora. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.860009"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10447","DOI":"10.1007\/s11356-017-0071-6","article-title":"Brevibacillus laterosporus isolated from the digestive tract of honeybees has high antimicrobial activity and promotes growth and productivity of honeybee\u2019s colonies","volume":"25","author":"Khaled","year":"2018","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1021\/acsomega.6b00513","article-title":"Diketopiperazines as Cross-Communication Quorum-Sensing Signals between Cronobacter sakazakii and Bacillus cereus","volume":"2","author":"Bofinger","year":"2017","journal-title":"ACS Omega"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jinendiran, S., Teng, W., Dahms, H.U., Liu, W., Ponnusamy, V.K., Chiu, C.C., Kumar, B.S.D., and Sivakumar, N. (2020). Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-70516-x"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.1016\/j.cell.2025.03.033","article-title":"Root microbiota regulates tiller number in rice","volume":"188","author":"Zhang","year":"2025","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1080\/14786419.2020.1753738","article-title":"Secondary metabolites of Galactomyces geotrichum from Laminaria japonica ameliorate cognitive deficits and brain oxidative stress in D-galactose induced Alzheimer\u2019s disease mouse model","volume":"35","author":"Wang","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Garc\u00eda, M., Ares-Arroyo, M., Wedel, E., Montero, N., Barbas, C., Rey-Stolle, M.F., Gonz\u00e1lez-Zorn, B., and Garc\u00eda, A. (2023). Multiplatform Metabolomics Characterization Reveals Novel Metabolites and Phospholipid Compositional Rules of Haemophilus influenzae Rd KW20. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241311150"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Li, J., Zhang, Q., Zhao, J., Zhang, H., and Chen, W. (2022). Streptococcus mutans and Candida albicans Biofilm Inhibitors Produced by Lactiplantibacillus plantarum CCFM8724. Curr. Microbiol., 79.","DOI":"10.1007\/s00284-022-02833-5"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s00284-012-0135-2","article-title":"Identification of antifungal compounds produced by Lactobacillus casei AST18","volume":"65","author":"Li","year":"2012","journal-title":"Curr. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"314","DOI":"10.4014\/jmb.2311.11006","article-title":"Antimicrobial Cyclic Dipeptides from Japanese Quail (Coturnix japonica) Eggs Supplemented with Probiotic Lactobacillus plantarum","volume":"34","author":"Kang","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Niranjan, R., Patil, S., Dubey, A., Lochab, B., and Priyadarshini, R. (2024). Small cyclic dipeptide produced by Lactobacillus rhamnosus with anti-biofilm properties against Streptococcus mutans biofilm. Biofilm, 8.","DOI":"10.1016\/j.bioflm.2024.100237"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s12088-020-00917-z","article-title":"Lactococcus lactis subsp. cremoris of Plant Origin Produces Antifungal Cyclo-(Leu-Pro) and Tetradecanoic Acid","volume":"61","author":"Gajbhiye","year":"2021","journal-title":"Indian J. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Delgado G\u00f3mez, L.M., Torres-Mendoza, D., Hern\u00e1ndez-Torres, K., Ortega, H.E., and Cubilla-Rios, L. (2023). Identification of Secondary Metabolites from the Mangrove-Endophyte Lasiodiplodia iranensis F0619 by UPLC-ESI-MS\/MS. Metabolites, 13.","DOI":"10.3390\/metabo13080912"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Liu, R., Shin, G., No, Y., Shin, J., Kang, S., and Park, P. (2025). Optimization of the Culture Conditions of Lactic Acid Bacteria for Antimicrobial Activity and Mass Production of Cyclic Dipeptides. J. Microbiol. Biotechnol., 35.","DOI":"10.4014\/jmb.2408.08007"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1007\/s42770-023-01081-4","article-title":"Limosilactobacillus reuteri as sustainable biological control agent against toxigenic Fusarium verticillioides","volume":"54","author":"Hirozawa","year":"2023","journal-title":"Braz. J. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1080\/14786419.2020.1756803","article-title":"Isolation of 2,5-diketopiperazines from Lysobacter capsici AZ78 with activity against Rhodococcus fascians","volume":"35","author":"Cimmino","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Stelmasiewicz, M., \u015awi\u0105tek, \u0141., and Ludwiczuk, A. (2023). Chemical and Biological Studies of Endophytes Isolated from Marchantia polymorpha. Molecules, 28.","DOI":"10.3390\/molecules28052202"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"No\u00ebl, A., Ferron, S., Rouaud, I., Gouault, N., Hurvois, J.P., and Tomasi, S. (2017). Isolation and Structure Identification of Novel Brominated Diketopiperazines from Nocardia ignorata\u2014A Lichen-Associated Actinobacterium. Molecules, 22.","DOI":"10.3390\/molecules22030371"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1080\/14786419.2019.1577834","article-title":"Four pairs of proline-containing cyclic dipeptides from Nocardiopsis sp. HT88, an endophytic bacterium of Mallotus nudiflorus L","volume":"34","author":"Xiang","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1007\/s12272-016-0751-7","article-title":"A new cyclic dipeptide penicimutide: The activated production of cyclic dipeptides by introduction of neomycin-resistance in the marine-derived fungus Penicillium purpurogenum G59","volume":"39","author":"Wang","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"571","DOI":"10.4014\/jmb.1907.07030","article-title":"Inhibition of Microbial Quorum Sensing Mediated Virulence Factors by Pestalotiopsis sydowiana","volume":"30","author":"Parasuraman","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Xiang, S.L., Xu, K.Z., Yin, L.J., and Jia, A.Q. (2024). An Investigation of Quorum Sensing Inhibitors against Bacillus cereus in The Endophytic Fungus Pithomyces sacchari of the Laurencia sp. Mar. Drugs., 22.","DOI":"10.3390\/md22040161"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Alves, B.V.B., Borges, L.J., Hanna, S.A., Soares, M.B.P., Bezerra, D.P., Moreira, L.L.P.F., Borges, W.S., Portela, R.W.D., Fernandez, C.C., and Umsza-Guez, M.A. (2025). Pigment Production by Pseudofusicoccum sp.: Extract Production, Cytotoxicity Activity, and Diketopiperazines Identified. Microorganisms, 13.","DOI":"10.3390\/microorganisms13020277"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/lam.12347","article-title":"Investigation of biotechnological potential of sponge-associated bacteria collected in Brazilian coast","volume":"60","author":"Santos","year":"2015","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhai, Y., Shao, Z., Cai, M., Zheng, L., Li, G., Yu, Z., and Zhang, J. (2019). Cyclo(l-Pro-l-Leu) of Pseudomonas putida MCCC 1A00316 Isolated from Antarctic Soil: Identification and Characterization of Activity against Meloidogyne incognita. Molecules, 24.","DOI":"10.3390\/molecules24040768"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s00284-002-3704-y","article-title":"Plant growth-promoting Pseudomonas putida WCS358 produces and secretes four cyclic dipeptides: Cross-talk with quorum sensing bacterial sensors","volume":"45","author":"Degrassi","year":"2002","journal-title":"Curr. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s42161-022-01225-9","article-title":"Bioactive extract of Pseudomonas sp. BC42 suppresses the infection stages of Colletotrichum orbiculare","volume":"104","author":"Kim","year":"2022","journal-title":"J. Plant Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1002\/ps.6470","article-title":"Biocontrol of the root-knot nematode Meloidogyne incognita by a nematicidal bacterium Pseudomonas simiae MB751 with cyclic dipeptide","volume":"77","author":"Sun","year":"2021","journal-title":"Pest. Manag. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11033-019-05102-0","article-title":"Chemical screening identifies an extract from marine Pseudomonas sp.-PTR-08 as an anti-aging agent that promotes fission yeast longevity by modulating the Pap1-ctt1+ pathway and the cell cycle","volume":"47","author":"Prastya","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s10482-017-0839-1","article-title":"Antibacterial low-molecular-weight compounds produced by the marine bacterium Rheinheimera japonica KMM 9513T","volume":"110","author":"Kalinovskaya","year":"2017","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_99","first-page":"372","article-title":"Studies on the Metabolic Products of Rosellinia necatrix Berlese: Part I. Isolation and Characterization of Several Physiologically Active Neutral Substances","volume":"24","author":"Chen","year":"1960","journal-title":"Bull. Agric. Chem. Soc. Japan"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kristiana, R., Cahyani, N.K.D., Jin, Y., Mudianta, I.W., Putri, F.R., Halisah, K.A.Z., Wang, M.X., Guo, Y.W., Li, X.W., and Radjasa, O.K. (2025). Antibacterial metabolites from a heterobranchia-associated bacteria and their prey from Bali, Indonesia. Curr. Res. Microb. Sci., 9.","DOI":"10.1016\/j.crmicr.2025.100448"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Romero-Diaz, C., Campos, S.M., Herrmann, M.A., Lewis, K.N., Williams, D.R., Soini, H.A., Novotny, M.V., Hews, D.K., and Martins, E.P. (2020). Structural Identification, Synthesis and Biological Activity of Two Volatile Cyclic Dipeptides in a Terrestrial Vertebrate. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61312-8"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ijfoodmicro.2014.09.029","article-title":"The involvement of bacterial quorum sensing in the spoilage of refrigerated Litopenaeus vannamei","volume":"192","author":"Zhu","year":"2015","journal-title":"Int. J. Food Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3923\/pjbs.2025.27.37","article-title":"Antibacterial and Anticancer Properties of Diketopiperazines from Streptomyces antimicrobicus BN122, an Endophyte in Oryza sativa var. glutinosa","volume":"28","author":"Taechowisan","year":"2025","journal-title":"Pak. J. Biol. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/12298093.2019.1635425","article-title":"Antifungal Activities of Streptomyces blastmyceticus Strain 12-6 Against Plant Pathogenic Fungi","volume":"47","author":"Kim","year":"2019","journal-title":"Mycobiology"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Kaaniche, F., Hamed, A., Elleuch, L., Chakchouk-Mtibaa, A., Smaoui, S., Karray-Rebai, I., Koubaa, I., Arcile, G., Allouche, N., and Mellouli, L. (2020). Purification and characterization of seven bioactive compounds from the newly isolated Streptomyces cavourensis TN638 strain via solid-state fermentation. Microb. Pathog., 142.","DOI":"10.1016\/j.micpath.2020.104106"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/08927010600780771","article-title":"Antifouling diketopiperazines produced by a deep-sea bacterium, Streptomyces fungicidicus","volume":"22","author":"Li","year":"2006","journal-title":"Biofouling"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.5650\/jos.ess20161","article-title":"Secondary Metabolites of an of Streptomyces griseorubens Isolate Are Predominantly Pyrrole- and Linoleic-acid like Compounds","volume":"69","author":"Arslan","year":"2020","journal-title":"J. Oleo Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/BF01936722","article-title":"Diketopiperazines containing L-proline from Streptomyces lavendulae and their stereochemistry in solution","volume":"33","author":"Kubo","year":"1977","journal-title":"Experientia"},{"key":"ref_109","first-page":"984","article-title":"Purification and identification of an antifungal agent from Streptomyces sp. KH-614 antagonistic to rice blast fungus, Pyricularia oryzae","volume":"13","author":"Rhee","year":"2003","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.ijantimicag.2004.05.005","article-title":"Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties","volume":"24","author":"Rhee","year":"2004","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Siddharth, S., and Vittal, R.R. (2018). Evaluation of antimicrobial, enzyme inhibitory, antioxidant and cytotoxic activities of partially purified volatile metabolites of marine Streptomyces sp. S2A. Microorganisms, 6.","DOI":"10.3390\/microorganisms6030072"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1080\/03758397.1960.10857698","article-title":"On the Mechanism of L-Prolyl Diketopiperazine Formation by Streptomyces","volume":"24","author":"Koaze","year":"1960","journal-title":"Bull. Agric. Chem. Soc. Japan"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/00021369.1964.10858285","article-title":"Isolation of Several Diketopiperazines from Peptone","volume":"28","author":"Tamura","year":"1964","journal-title":"Agric. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Bhandari, S., Bhattarai, B.R., Adhikari, A., Aryal, B., Shrestha, A., Aryal, N., Lamichhane, U., Thapa, R., Thapa, B.B., and Yadav, R.P. (2022). Characterization of Streptomyces Species and Validation of Antimicrobial Activity of Their Metabolites through Molecular Docking. Processes, 10.","DOI":"10.3390\/pr10102149"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.4014\/jmb.1608.08032","article-title":"Isolation, Purification, and Characterization of Five Active Diketopiperazine Derivatives from Endophytic Streptomyces SUK 25 with Antimicrobial and Cytotoxic Activities","volume":"27","author":"Alshaibani","year":"2017","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Buedenbender, L., Robertson, L.P., Lucantoni, L., Avery, V.M., Kurtb\u00f6ke, D.\u0130., and Carroll, A.R. (2018). HSQC-TOCSY Fingerprinting-Directed Discovery of Antiplasmodial Polyketides from the Marine Ascidian-Derived Streptomyces sp. (USC-16018). Mar. Drugs, 16.","DOI":"10.3390\/md16060189"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2174\/1874847301705010023","article-title":"Marine sp. VITMK1 Derived Pyrrolo [1, 2-A] Pyrazine-1, 4-Dione, Hexahydro-3-(2-Methylpropyl) and Its Free Radical Scavenging Activity","volume":"5","author":"Manimaran","year":"2017","journal-title":"Open Bioact. Compd. J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.phytol.2018.04.014","article-title":"Bioactive aromatic metabolites from the sea urchin-derived actinomycete Streptomyces spectabilis strain HDa1","volume":"25","author":"Guo","year":"2018","journal-title":"Phytochem. Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.anaerobe.2018.06.005","article-title":"Identification of an early stage biofilm inhibitor from Veillonella tobetsuensis","volume":"52","author":"Mashima","year":"2018","journal-title":"Anaerobe"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1750-3841.2009.01062.x","article-title":"2,5-diketopiperazines (cyclic dipeptides) in beef: Identification, synthesis, and sensory evaluation","volume":"74","author":"Chen","year":"2009","journal-title":"J. Food Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"185","DOI":"10.47665\/tb.39.2.006","article-title":"Fagonia cretica: Identification of compounds in bioactive gradient high performance liquid chromatography fractions against multidrug resistant human gut pathogens","volume":"39","author":"Tabassum","year":"2022","journal-title":"Trop. Biomed."},{"key":"ref_122","first-page":"2852","article-title":"Constituents of Gymnadenia conopsea","volume":"35","author":"Yue","year":"2010","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1021\/jf9700992","article-title":"Chemical Characterization of Diketopiperazines in Beer","volume":"45","author":"Gautschi","year":"1997","journal-title":"J. Agric. Food Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1021\/jf991256v","article-title":"Identification of Proline-Based Diketopiperazines in Roasted Coffee","volume":"48","author":"Ginz","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.aca.2020.10.054","article-title":"Fractionation platform for target identification using off-line directed two-dimensional chromatography, mass spectrometry and nuclear magnetic resonance","volume":"1142","author":"Elfrink","year":"2021","journal-title":"Anal. Chim. Acta."},{"key":"ref_126","first-page":"67","article-title":"The Himalayan ethnic beverage tongba with therapeutic properties in high-altitude illnesses and metabolomic similarities to Japanese sake","volume":"15","author":"Majumder","year":"2022","journal-title":"Acta Univ. Sapientiae Aliment."},{"key":"ref_127","first-page":"261","article-title":"In silico insights into the efficacy of Djareeling Himalaya\u2019s traditional fermented beverages to combat various high-altitude sicknesses","volume":"27","author":"Majumder","year":"2023","journal-title":"Acta Univ. Cibiniensis Ser. E"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"9563","DOI":"10.1021\/jf902033v","article-title":"Detection and quantitation of 2,5-diketopiperazines in wheat sourdough and bread","volume":"57","author":"Ryan","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Agarwal, P., Fischer, H.D., Camalle, M.D., and Skirycz, A. (2025). Not to be overlooked: Dipeptides and their role in plant stress resilience. J. Exp. Bot., online ahead of print.","DOI":"10.1093\/jxb\/eraf311"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Wei, B., Ying, T.T., Lv, H.W., Zhou, Z.Y., Cai, H., Hu, G.A., Liang, H.M., Yu, W.C., Yu, Y.L., and Fan, A.L. (2025). Global analysis of fungal biosynthetic gene clusters reveals the diversification of diketopiperazine biosynthesis. Bioresour. Technol., 422.","DOI":"10.1016\/j.biortech.2025.132218"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1007\/s00248-016-0896-4","article-title":"Non-ribosomal Peptide Synthases from Pseudomonas aeruginosa Play a Role in Cyclodipeptide Biosynthesis, Quorum-Sensing Regulation, and Root Development in a Plant Host","volume":"73","year":"2017","journal-title":"Microb. Ecol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"9923","DOI":"10.1016\/j.tet.2007.04.105","article-title":"Diketopiperazines: Biological activity and synthesis","volume":"63","author":"Martins","year":"2007","journal-title":"Tetrahedron"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1021\/cb900165y","article-title":"New and unexpected insights into the modulation of LuxR-type quorum sensing by cyclic dipeptides","volume":"4","author":"Campbell","year":"2009","journal-title":"ACS Chem. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Domzalski, A., Margent, L., Vigo, V., Dewan, F., Pilarsetty, N.V.K., Xu, Y., and Kawamura, A. (2021). Unambiguous Stereochemical Assignment of Cyclo(Phe-Pro), Cyclo(Leu-Pro), and Cyclo(Val-Pro) by Electronic Circular Dichroic Spectroscopy. Molecules, 26.","DOI":"10.3390\/molecules26195981"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1021\/acsagscitech.5c00236","article-title":"Antimicrobial and Antifungal Activities of Proline-Based 2,5-Diketopiperazines Occurring in Food and Beverages and Their Synergism with Lactic Acid","volume":"5","author":"Koval","year":"2025","journal-title":"ACS Agric. Sci. Technol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3985","DOI":"10.1021\/ja00819a042","article-title":"Studies on cyclic dipeptides. I. Thermodynamics of the cis-trans isomerization of the side chains in cyclic dipeptides","volume":"96","author":"Eguchi","year":"1974","journal-title":"J. Am. Chem. Soc."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Ying, J., Lin, R., Xu, P., Wu, Y., Liu, Y., and Zhao, Y. (2018). Prebiotic formation of cyclic dipeptides under potentially early Earth conditions. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19335-9"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Guo, Y., Zhang, Y., Ying, J., Liu, Y., Zhang, G., and Zhao, Y. (2022). Selection of Amino Acid Chirality Induced by Cyclic Dipeptide Synthesis in Plausible Prebiotic Conditions. Front. Astron. Space Sci., 9.","DOI":"10.3389\/fspas.2022.794932"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Chi, Y., Li, X., Chen, Y., Zhang, Y., Liu, Y., Gao, X., and Zhao, Y. (2022). Prebiotic Formation of Catalytically Active Dipeptides via Trimetaphosphate Activation. Chem. Asian J., 17.","DOI":"10.1002\/asia.202200926"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1080\/09168451.2019.1659718","article-title":"Investigation of the formation mechanism of proline-containing cyclic dipeptide from the linear peptide","volume":"83","author":"Otsuka","year":"2019","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Bojarska, J., Mieczkowski, A., Ziora, Z.M., Skwarczynski, M., Toth, I., Shalash, A.O., Parang, K., El-Mowafi, S.A., Mohammed, E.H.M., and Elnagdy, S. (2021). Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold. Biomolecules., 11.","DOI":"10.3390\/biom11101515"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4399","DOI":"10.1039\/C5OB00023H","article-title":"A benzotriazole-mediated route to protected marine-derived hetero-2,5-diketopiperazines containing proline","volume":"13","author":"Nsengiyumva","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1007\/s00253-022-12004-y","article-title":"One-pot synthesis of 2,5-diketopiperazine with high titer and versatility using adenylation enzyme","volume":"106","author":"Karakama","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Kano, S., Suzuki, S., Hara, R., and Kino, K. (2019). Synthesis of d-Amino Acid-Containing Dipeptides Using the Adenylation Domains of Nonribosomal Peptide Synthetase. Appl. Environ. Microbiol., 85.","DOI":"10.1128\/AEM.00120-19"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1021\/acs.joc.5c00097","article-title":"Synthesis of Mono-Boc-2,5-Diketopiperazine: A Key Building Block for Amide and Peptide Synthesis","volume":"90","author":"Ramakrishna","year":"2025","journal-title":"J. Org. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/psc.1139","article-title":"Regioselective and sequential reactivity of activated 2,5-diketopiperazines","volume":"15","author":"Farran","year":"2009","journal-title":"J. Pept. Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1021\/cc0600876","article-title":"Microwave-assisted solid-phase synthesis of 2,5-diketopiperazines: Solvent and resin dependence","volume":"8","author":"Tullberg","year":"2006","journal-title":"J. Comb. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1021\/jo0619635","article-title":"Synthesis of functionalized, unsymmetrical 1,3,4,6-tetrasubstituted 2,5-diketopiperazines","volume":"72","author":"Tullberg","year":"2007","journal-title":"J. Org. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/psc.446","article-title":"Diketopiperazines in peptide and combinatorial chemistry","volume":"9","author":"Fischer","year":"2003","journal-title":"J. Pept. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1021\/jf062029d","article-title":"Antioxidant constituents in distillation residue of Awamori spirits","volume":"55","author":"Takaya","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/j.bmc.2012.01.050","article-title":"Cyclic dipeptides exhibit potency for scavenging radicals","volume":"20","author":"Furukawa","year":"2012","journal-title":"Bioorg Med. Chem."},{"key":"ref_152","first-page":"162","article-title":"Marine Cyclic Dipeptide Cyclo (L-Leu-L-Pro) Protects Normal Breast Epithelial Cells from tBHP-induced Oxidative Damage by Targeting CD151","volume":"8","author":"Deepak","year":"2021","journal-title":"Arch. Breast Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.bbamem.2017.04.009","article-title":"Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation","volume":"1859","author":"Gowrishankar","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.fct.2018.11.013","article-title":"Quorum quelling efficacy of marine cyclic dipeptide -cyclo(L-leucyl-L-prolyl) against the uropathogen Serratia marcescens","volume":"123","author":"Gowrishankar","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Li, L., Xu, Z., Cao, R., Li, J., Wu, C.J., Wang, Y., and Zhu, H. (2023). Effects of hydroxyl group in cyclo(Pro-Tyr)-like cyclic dipeptides on their anti-QS activity and self-assembly. iScience, 26.","DOI":"10.1016\/j.isci.2023.107048"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Jothi, R., Hari Prasath, N., Gowrishankar, S., and Pandian, S.K. (2021). Bacterial Quorum-Sensing Molecules as Promising Natural Inhibitors of Candida albicans Virulence Dimorphism: An In Silico and In Vitro Study. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.781790"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/lam.13424","article-title":"Role of RpoS in stress resistance, biofilm formation and quorum sensing of Shewanella baltica","volume":"72","author":"Zhang","year":"2021","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Paopradit, P., Tansila, N., Surachat, K., and Mittraparp-Arthorn, P. (2021). Vibrio alginolyticus influences quorum sensing-controlled phenotypes of acute hepatopancreatic necrosis disease-causing Vibrio parahaemolyticus. PeerJ, 9.","DOI":"10.7717\/peerj.11567"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"25291","DOI":"10.1021\/acsomega.2c02202","article-title":"Quorum Sensing Inhibitory and Quenching Activity of Bacillus cereus RC1 Extracts on Soft Rot-Causing Bacteria Lelliottia amnigena","volume":"7","author":"Kachhadia","year":"2022","journal-title":"ACS Omega"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1016\/j.bmc.2018.11.042","article-title":"Anti-biofilm and anti-adherence properties of novel cyclic dipeptides against oral pathogens","volume":"27","author":"Simon","year":"2019","journal-title":"Bioorganic Med. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1177\/0022034515594779","article-title":"Association of Synergistetes and Cyclodipeptides with Periodontitis","volume":"94","author":"Marchesan","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Wu, M., Huang, S., Du, J., Li, Y., Jiang, S., Zhan, L., and Huang, X. (2022). D-alanylation of lipoteichoic acid contributes to biofilm formation and acidogenesis capacity of Streptococcus mutans. Microb. Pathog., 169.","DOI":"10.1016\/j.micpath.2022.105666"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/omi.70000","article-title":"Marine-Derived Cyclo(l-Leucyl-l-Prolyl) Targets d-Alanylation of Lipoteichoic Acid to Combat Streptococcus mutans UA159 Mediated Dental Cariogenesis","volume":"40","author":"Sangavi","year":"2025","journal-title":"Mol. Oral. Microbiol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/02652030802403760","article-title":"Isolation of microorganisms and substances inhibitory to aflatoxin production","volume":"25","author":"Yabe","year":"2008","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/bip.1976.360150905","article-title":"Influence of D and L amino-acid residues on the conformation of peptides in solution: A carbon-13 nuclear magnetic resonance study of cyclo(prolyl-leucyl)","volume":"15","author":"Deslauriers","year":"1976","journal-title":"Biopolymers"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Okuda-Shimazaki, J., Yoshida, H., and Sode, K. (2020). AD dependent glucose dehydrogenases\u2014Discovery and engineering of representative glucose sensing enzymes. Bioelectrochemistry, 132.","DOI":"10.1016\/j.bioelechem.2019.107414"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Yoshida, H., Sakai, G., Mori, K., Kojima, K., Kamitori, S., and Sode, K. (2015). Structural analysis of fungus-derived FAD glucose dehydrogenase. Sci. Rep., 5.","DOI":"10.1038\/srep13498"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Salman, M., Tariq, A., Ijaz, A., Naheed, S., Hashem, A., Abd Allah, E.F., Soliman, M.H., and Javed, M.R. (2020). In Vitro Antimicrobial and Antioxidant Activities of Lactobacillus coryniformis BCH-4 Bioactive Compounds and Determination of their Bioprotective Effects on Nutritional Components of Maize (Zea mays L.). Molecules, 25.","DOI":"10.3390\/molecules25204685"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Iimura, K., Furukawa, T., Yamamoto, T., Negishi, L., Suzuki, M., and Sakuda, S. (2017). The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus. Toxins, 9.","DOI":"10.3390\/toxins9070219"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s11033-020-05281-1","article-title":"Characterization of antifungal metabolites produced by Lactobacillus plantarum and Lactobacillus coryniformis isolated from rice rinsed water","volume":"47","author":"Bukhari","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Ahmad, S.J., Abdul Rahim, M.B.H., Baharum, S.N., Baba, M.S., and Zin, N.M. (2017). Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach. J. Trop. Med., 2017.","DOI":"10.1155\/2017\/2189814"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Ceravolo, I.P., Leoni, L.F., Krettli, A.U., Murta, S.M.F., Resende, D.M., Cruz, M.G.F.M.L., Varej\u00e3o, J.O.S., Mendes, L.L., Varej\u00e3o, E.V.V., and Kohlhoff, M. (2024). Novel 2,5-Diketopiperazines with In Vitro Activities against Protozoan Parasites of Tropical Diseases. Pharmaceuticals, 17.","DOI":"10.3390\/ph17020223"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Malla, R., Marni, R., and Chakraborty, A. (2023). Exploring the role of CD151 in the tumor immune microenvironment: Therapeutic and clinical perspectives. Biochim. Biophys. Acta Rev. Cancer, 1878.","DOI":"10.1016\/j.bbcan.2023.188898"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Erfani, S., Hua, H., Pan, Y., Zhou, B.P., and Yang, X.H. (2021). The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis. Cancers, 13.","DOI":"10.3390\/cancers13092005"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Gao, X., Liu, S., Cao, Y., Shi, L., and Yin, Y. (2025). The controversial role of CD151 in different solid tumors: Promoter or suppressor?. Cancer Cell Int., 25.","DOI":"10.1186\/s12935-025-03751-9"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Shanmukhappa, K., Kim, J.K., and Kapil, S. (2007). Role of CD151, A tetraspanin, in porcine reproductive and respiratory syndrome virus infection. Virol. J., 4.","DOI":"10.1186\/1743-422X-4-62"},{"key":"ref_177","first-page":"4811","article-title":"CD151 confers metastatic potential to clear cell sarcoma of the soft tissue in animal model","volume":"17","author":"Kawashima","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1042\/BST0390553","article-title":"Tetraspanin CD151 as a target for antibody-based cancer immunotherapy","volume":"39","author":"Haeuw","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Marni, R., Kundrapu, D.B., Chakraborti, A., and Malla, R. (2022). Insight into drug sensitizing effect of diallyl disulfide and diallyl trisulfide from Allium sativum L. on paclitaxel-resistant triple-negative breast cancer cells. J. Ethnopharmacol., 296.","DOI":"10.1016\/j.jep.2022.115452"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Akella, M., and Malla, R. (2020). Molecular modeling and in vitro study on pyrocatechol as potential pharmacophore of CD151 inhibitor. J. Mol. Graph. Model., 100.","DOI":"10.1016\/j.jmgm.2020.107681"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Akella, M., Amajala, K.C., and Malla, R.R. (2019). Bioinformatics analysis of regulatory elements of the CD151 gene and insilico docking of CD151 with diallyl sulfide. Gene Rep., 17.","DOI":"10.1016\/j.genrep.2019.100551"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.procbio.2017.12.004","article-title":"A novel small molecule inhibitor of CD151 inhibits proliferation of metastatic triple negative breast cancer cell lines","volume":"66","author":"Gavara","year":"2018","journal-title":"Process Biochem."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Kgk, D., Kumari, S., G, S., and Malla, R.R. (2020). Marine natural compound cyclo(L-leucyl-L-prolyl) peptide inhibits migration of triple negative breast cancer cells by disrupting interaction of CD151 and EGFR signaling. Chem. Biol. Interact., 315.","DOI":"10.1016\/j.cbi.2019.108872"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Wong, A.H., Nga, M.E., Chin, C.Y., Tai, Y.K., Wong, H.C., Soo, R., An, O., Yang, H., Seet, J.E., and Lim, Y.C. (2024). Impact of CD151 overexpression on prognosis and therapy in non-small cell lung cancer patients lacking EGFR mutations. Cell Prolif., 57.","DOI":"10.1111\/cpr.13708"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Zhu, J., Cai, T., Zhou, J., Du, W., Zeng, Y., Liu, T., Fu, Y., Li, Y., Qian, Q., and Yang, X.H. (2021). CD151 drives cancer progression depending on integrin \u03b13\u03b21 through EGFR signaling in non-small cell lung cancer. J. Exp. Clin. Cancer Res., 40.","DOI":"10.1186\/s13046-021-01998-4"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.2174\/0929867329666220801143650","article-title":"2,5-Diketopiperazines: A Review of Source, Synthesis, Bioactivity, Structure, and MS Fragmentation","volume":"30","author":"Jia","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Song, Z., Hou, Y., Yang, Q., Li, X., and Wu, S. (2021). Structures and Biological Activities of Diketopiperazines from Marine Organisms: A Review. Mar. Drugs, 19.","DOI":"10.3390\/md19080403"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.2174\/092986712801323243","article-title":"Antimicrobial and biofilm inhibiting diketopiperazines","volume":"19","author":"Abraham","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Ding, L., Xu, P., Zhang, W., Yuan, Y., He, X., Su, D., Shi, Y., Naman, C.B., Yan, X., and Wu, B. (2020). Three New Diketopiperazines from the Previously Uncultivable Marine Bacterium Gallaecimonas mangrovi HK-28 Cultivated by iChip. Chem. Biodivers., 17.","DOI":"10.1002\/cbdv.202000221"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/10\/397\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:17:15Z","timestamp":1760242635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/10\/397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":189,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["md23100397"],"URL":"https:\/\/doi.org\/10.3390\/md23100397","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]}}}