{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:23:25Z","timestamp":1774344205979,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Most studies on the Arthrosphaera genus, or giant pill millipedes, focus on its taxonomy, distribution, and ecology. Therefore, this investigation aimed to explore the chemical composition and bioactive properties of the hemolymph of the giant pill millipede Arthrosphaera lutescens (Butler, 1872). Chemical characterization of hemolymph was performed using gas chromatography\u2013mass spectrometry (GC-MS) and liquid chromatography\u2013quadrupole time-of-flight mass spectrometry (LC-MS Q-TOF), revealing a complex array of over 200 compounds. The bioactive properties of hemolymph were determined by using radical scavenging capacity (DPPH assay); antibacterial activity against human pathogens like Escherichia coli (Migula, 1895) Castellani and Chalmers 1919, Klebsiella pneumonia (Schroeter, 1886) Trevisan 1887, and Staphylococcus aureus (Rosenbach, 1884); and cytotoxicity against Dalton\u2019s lymphoma ascites (DLA) cells using the trypan blue assay. The hemolymph showed radical scavenging properties and antibacterial and cytotoxic activity. Among the identified metabolites, 1,2-dimethoxy-13-methyl-[1,3]benzodioxolo[5,6-c]phenanthridine (DMBP) emerged as a promising candidate due to its high abundance and bioactivity profile, showcasing therapeutic potential against both lymphoma and S. aureus in further docking studies. Computational analysis identified key T-cell lymphoma targets, with molecular docking suggesting DMBP\u2019s anticancer properties through interactions with proteins like AKT1 and mTOR. Additionally, docking revealed DMBP\u2019s antibacterial effects via interactions with proteins such as Sortase-A and DNA gyrase. This research underscores the potential pharmaceutical applications of metabolites from giant pill millipedes.<\/jats:p>","DOI":"10.3390\/cimb47060434","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Hemolymph of the Pill Millipede Arthrosphaera lutescens (Butler, 1872): Chemical Composition, Bioactive Properties, and Computational Studies"],"prefix":"10.3390","volume":"47","author":[{"given":"Priyanka","family":"Palakkaparambil","sequence":"first","affiliation":[{"name":"Division of Biomaterial Sciences, Department of Zoology, Sree Neelakanta Government Sanskrit College (Affiliated to University of Calicut), Pattambi, Palakkad 679306, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9211-6962","authenticated-orcid":false,"given":"Veena","family":"Venugopal","sequence":"additional","affiliation":[{"name":"Division of Biomaterial Sciences, Department of Zoology, Sree Neelakanta Government Sanskrit College (Affiliated to University of Calicut), Pattambi, Palakkad 679306, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gouthami","family":"Vijayan","sequence":"additional","affiliation":[{"name":"Department of Botany, Sree Neelakanta Government Sanskrit College, Pattambi, Palakkad 679306, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1986-0855","authenticated-orcid":false,"given":"Mohammed Amjed","family":"Alsaegh","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varun","family":"Thachan Kundil","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Microbiology, Kannur University, Kannur 670661, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun Kumar","family":"Gangadharan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Kannur University, Kannur 670661, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2010-9351","authenticated-orcid":false,"given":"Ovungal","family":"Sabira","sequence":"additional","affiliation":[{"name":"Division of Biomaterial Sciences, Department of Zoology, Sree Neelakanta Government Sanskrit College (Affiliated to University of Calicut), Pattambi, Palakkad 679306, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Aswathi","sequence":"additional","affiliation":[{"name":"Division of Biomaterial Sciences, Department of Zoology, Sree Neelakanta Government Sanskrit College (Affiliated to University of Calicut), Pattambi, Palakkad 679306, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6227-9658","authenticated-orcid":false,"given":"A. V.","family":"Raghu","sequence":"additional","affiliation":[{"name":"Kerala Forest Research Institute, Peechi, Thrissur 680653, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-8853","authenticated-orcid":false,"given":"Kodangattil","family":"Narayanan Jayaraj","sequence":"additional","affiliation":[{"name":"Basic Medical and Dental Sciences Department, Centre for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-0245","authenticated-orcid":false,"given":"Anthyalam Parambil","family":"Ajaykumar","sequence":"additional","affiliation":[{"name":"Division of Biomaterial Sciences, Department of Zoology, Sree Neelakanta Government Sanskrit College (Affiliated to University of Calicut), Pattambi, Palakkad 679306, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S1002-0160(08)60070-3","article-title":"Distribution of Pill Millipedes (Arthrosphaera) and Associated Soil Fauna in the Western Ghats and West Coast of India","volume":"18","author":"Ashwini","year":"2008","journal-title":"Pedosphere"},{"key":"ref_2","unstructured":"Wesener, T. (2016). The Giant Pill-Millipedes, Order Sphaerotheriida: An Annotated Species Catalogue with Morphological Atlas and List of Apomorphies (Arthropoda: Diplopoda), Zoologisches Forschungsmuseum Koenig\u2014Leibniz-Institut f\u00fcr Biodiversit\u00e4t der Tiere. Available online: https:\/\/exuvium.net\/wp-content\/uploads\/2022\/12\/giant_pill_millipedes-sphaerotheriida_-species_catalogue.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1439-0469.1984.tb00559.x","article-title":"Phylogeny of Millipedes\u2014A Cladistic Analysis","volume":"22","author":"Enghoff","year":"2009","journal-title":"J. Zool. Syst. Evol. Res."},{"key":"ref_4","first-page":"41","article-title":"The Group Taxonomy and Geography of the Sphaerotheriida (Diplopoda)","volume":"Volume 32","author":"Jeekel","year":"1974","journal-title":"Symposia of the Zoological Society of London"},{"key":"ref_5","first-page":"557","article-title":"The Giant Pill-Millipedes of Madagascar","volume":"56","author":"Wesener","year":"2005","journal-title":"Proc. Calif. Acad. Sci."},{"key":"ref_6","first-page":"269","article-title":"A Monograph of the Pill Millipedes Zephroniidae Inhabiting India, Ceylon and Burma","volume":"12","author":"Pocock","year":"1899","journal-title":"J. Bombay Nat. Hist. Soc."},{"key":"ref_7","first-page":"181","article-title":"Morphological Features of Three Endemic Pill-Millipedes of the Genus Arthrosphaera in the Western Ghats of India","volume":"3","author":"Kadamannaya","year":"2012","journal-title":"Anim. Biol."},{"key":"ref_8","first-page":"168","article-title":"Millipedes as Ecosystem Engineers: Their Role in Nutrient Cycling, Soil Health and Biotechnological Significance","volume":"9","author":"Yashwant","year":"2024","journal-title":"Int. J. Entomol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Klowden, M.J., and Palli, S.R. (2023). Chapter 7\u2014Circulatory Systems. Physiological Systems in Insects (Fourth Edition), Academic Press.","DOI":"10.1016\/B978-0-12-820359-0.00010-4"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/pmic.201500427","article-title":"Comparative Proteomics Analysis of Silkworm Hemolymph during the Stages of Metamorphosis via Liquid Chromatography and Mass Spectrometry","volume":"16","author":"Hou","year":"2016","journal-title":"Proteomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF00692300","article-title":"Patterns of Hemolymph Osmoregulation in Three Desert Arthropods","volume":"112","author":"Riddle","year":"1976","journal-title":"J. Comp. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1139\/z78-201","article-title":"Seasonal Changes in Hemolymph Amino Acids, Proteins, and Inorganic Ions of a Desert Millipede Orthoporus Ornatus (Girard) (Diplopoda: Spirostreptidae)","volume":"56","author":"Pugach","year":"1978","journal-title":"Can. J. Zool."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0305-0491(71)90280-X","article-title":"On the Free Amino Acids in the Haemolymph of a Millipede","volume":"38","author":"Nair","year":"1971","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_14","first-page":"431","article-title":"Physico-Chemical Properties of Haemolymph of Chilopoda and Diplopoda (Myriapoda, Arthropoda): Protein Content, pH, Osmolarity","volume":"81","author":"Xylander","year":"2009","journal-title":"Soil Org."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/0300-9629(89)90497-0","article-title":"Composition of the Hemolymph of Mygalomorph Spiders (Orthognatha)","volume":"93","author":"Punzo","year":"1989","journal-title":"Comp. Biochem. Physiol. A"},{"key":"ref_16","first-page":"98","article-title":"Seperation of Bioactive Compounds from Haemolymph of Scarab Beetle Scarabaeus Sacer (Coleoptera: Scarabaeidae) by GC-MS and Determination of Its Antimicrobial Activity","volume":"5","author":"Mohamed","year":"2021","journal-title":"Int. J. Appl. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, Z.-L., Xu, H.-N., Gong, C.-M., Li, Y.-Z., Song, X.-M., Li, Y.-M., Zhang, D.-D., and Wang, R. (2024). Microorganism-Derived Bisindole Alkaloids With Anticancer Potential and Their Mechanisms: A Comprehensive Review. Chem. Biodivers., 22.","DOI":"10.1002\/cbdv.202402398"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.phymed.2013.09.001","article-title":"Antioxidant and Intestinal Anti-Inflammatory Effects of Plant-Derived Coumarin Derivatives","volume":"21","author":"Witaicenis","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sabira, O., Vignesh, A.R., Ajaykumar, A.P., Varma, S.R., Jayaraj, K.N., Sebastin, M., Nikhila, K., Babu, A., Rasheed, V.A., and Binitha, V.S. (2022). The Chemical Composition and Antimitotic, Antioxidant, Antibacterial and Cytotoxic Properties of the Defensive Gland Extract of the Beetle, Luprops Tristis Fabricius. Molecules, 27.","DOI":"10.3390\/molecules27217476"},{"key":"ref_20","unstructured":"(2025, February 06). SwissTargetPrediction. Available online: http:\/\/www.swisstargetprediction.ch\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"CP Bioinform."},{"key":"ref_22","unstructured":"(2025, February 06). GeneCards\u2014Human Genes|Gene Database|Gene Search. Available online: https:\/\/www.genecards.org\/."},{"key":"ref_23","unstructured":"(2025, February 06). DISGENET: Genomics Platform for Precision Medicine. Available online: https:\/\/www.disgenet.com."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D514","DOI":"10.1093\/nar\/gki033","article-title":"Online Mendelian Inheritance in Man (OMIM), a Knowledgebase of Human Genes and Genetic Disorders","volume":"33","author":"Hamosh","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_25","unstructured":"(2025, February 06). Draw Venn Diagram. Available online: https:\/\/bioinformatics.psb.ugent.be\/webtools\/Venn\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein-Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: Identifying Hub Objects and Sub-Networks from Complex Interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/pmic.201400515","article-title":"FunRich: An Open Access Standalone Functional Enrichment and Interaction Network Analysis Tool","volume":"15","author":"Pathan","year":"2015","journal-title":"Proteomics"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Haridas, M., Abdulhameed, S., Francis, D., and Kumar, S.S. (2024). Drugs from Nature: Targets, Assay Systems and Leads, Springer Nature.","DOI":"10.1007\/978-981-99-9183-9"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7106","DOI":"10.1021\/acs.jctc.1c00810","article-title":"Efficient Exploration of Chemical Space with Docking and Deep Learning","volume":"17","author":"Yang","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/07391102.2020.1813200","article-title":"Repurposing Simeprevir, Calpain Inhibitor IV and a Cathepsin F Inhibitor against SARS-CoV-2 and Insights into Their Interactions with Mpro","volume":"40","author":"Abhithaj","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_33","first-page":"e000159","article-title":"GC-MS Analysis of Bioactive Compounds from Melastomastrum Capitatum (Vahl) Fern. Leaf Methanol Extract: An Anticancer Plant","volume":"3","author":"Ukwubile","year":"2019","journal-title":"Sci. Afr."},{"key":"ref_34","unstructured":"(2025, April 09). (9Z)-octadecen-1-ol (CHEBI:73504). Available online: https:\/\/www.ebi.ac.uk\/chebi\/searchId.do?chebiId=73504."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"130","DOI":"10.4014\/jmb.2008.08027","article-title":"Undecanoic Acid, Lauric Acid, and N-Tridecanoic Acid Inhibit Escherichia Coli Persistence and Biofilm Formation","volume":"31","author":"Jin","year":"2021","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_36","unstructured":"Duke, J.A. (2024, December 10). Duke\u2019s Phytochemical and Ethnobotanical Databases, Available online: https:\/\/phytochem.nal.usda.gov\/."},{"key":"ref_37","first-page":"246","article-title":"Cytotoxic Activity of Bioactive Compound 1, 2- Benzene Dicarboxylic Acid, Mono 2- Ethylhexyl Ester Extracted from a Marine Derived Streptomyces Sp. VITSJK8","volume":"3","author":"Krishnan","year":"2014","journal-title":"Int. J. Mol. Cell Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"114235","DOI":"10.1016\/j.jep.2021.114235","article-title":"Chemical Profiling and In-Vitro Anti-Inflammatory Activity of Bioactive Fraction(s) from Trichodesma Indicum (L.) R.Br. against LPS Induced Inflammation in RAW 264.7 Murine Macrophage Cells","volume":"279","author":"Hamsalakshmi","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"030098","DOI":"10.1063\/5.0053057","article-title":"Phytochemical Analysis of Bioactive Compounds in Ethanolic Extract of Sterculia Quadrifida R.Br","volume":"2353","author":"Siswadi","year":"2021","journal-title":"AIP Conf. Proc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/0167-4781(96)00121-2","article-title":"Fatty Acids Selectively Inhibit Eukaryotic DNA Polymerase Activities in Vitro","volume":"1308","author":"Mizushina","year":"1996","journal-title":"Biochim. Biophys. Acta Gene Struct. Express."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF00696269","article-title":"Fatty Acid Pattern of Haemolymph Lipids in Spodoptera Littoralis Boisduval Larvae","volume":"93","author":"Boctor","year":"1974","journal-title":"J. Comp. Physiol. B"},{"key":"ref_42","first-page":"59","article-title":"GC-MS Determination of Bioactive Constituents of Giant African Snail (Archachatina Maginata) Haemolymph","volume":"10","author":"Lawal","year":"2015","journal-title":"J. Pharmacol. Biol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/jemt.20660","article-title":"The Defensive Secretion of Carabus Lefebvrei Dejean 1826 Pupa (Coleoptera, Carabidae): Gland Ultrastructure and Chemical Identification","volume":"72","author":"Giglio","year":"2009","journal-title":"Microsc. Res. Tech."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1002\/cbic.201800809","article-title":"Fatty Acid Biosynthesis: Chain-Length Regulation and Control","volume":"20","author":"Heil","year":"2019","journal-title":"ChemBioChem"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0022-1910(95)00106-9","article-title":"Levels of Hemolymph Sugars and Body Glycogen of Honeybees (Apis mellifera L.) from Colonies Preparing to Swarm","volume":"42","author":"Leta","year":"1996","journal-title":"J. Insect Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0065-2806(03)31004-5","article-title":"Trehalose\u2014The Insect \u2018Blood\u2019 Sugar","volume":"Volume 31","author":"Thompson","year":"2003","journal-title":"Advances in Insect Physiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0022-1910(02)00267-6","article-title":"The Role of Hemolymph Proline as a Nitrogen Sink during Blood Meal Digestion by the Mosquito Aedes aegypti","volume":"49","author":"Pennington","year":"2003","journal-title":"J. Insect Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1086\/665406","article-title":"Quantitative Assessment of Hemolymph Metabolites in Two Physiological States and Two Populations of the Land Snail Helix pomatia","volume":"85","author":"Nicolai","year":"2012","journal-title":"Physiol. Biochem. Zool."},{"key":"ref_49","first-page":"1","article-title":"Chemical Components and Cardiovascular Activities of Valeriana spp.","volume":"2015","author":"Chen","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_50","first-page":"069817","article-title":"Defense Mechanisms of Arthropods. XI. The Structure, Function, and Phenolic Secretions of the Glands of a Chordeumoid Millipede and a Carabid Beetle","volume":"70","author":"Eisner","year":"1963","journal-title":"Psyche (Camb. Mass.)"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bse.2015.04.033","article-title":"The Chemical Defenses of Millipedes (Diplopoda): Biochemistry, Physiology and Ecology","volume":"61","author":"Shear","year":"2015","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.aninu.2023.03.006","article-title":"Research Progress on Anti-Stress Nutrition Strategies in Swine","volume":"13","author":"Wang","year":"2023","journal-title":"Anim. Nutr."},{"key":"ref_53","unstructured":"Dettner, K. (2015). Toxins, Defensive Compounds and Drugs from Insects. Insect Molecular Biology and Ecology, CRC Press."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"448","DOI":"10.4001\/003.026.0448","article-title":"Identification and Molecular Characterisation of a Novel Manganese Superoxide Dismutase Gene from Flesh Fly Larvae, Sarcophaga Argyrostoma (Diptera: Sarcophagidae)","volume":"26","author":"Mahmoud","year":"2018","journal-title":"Afr. Entomol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Shalaby, E. (2019). Flavonoids and Phenolic Acids as Potential Natural Antioxidants. Antioxidants, IntechOpen.","DOI":"10.5772\/intechopen.77838"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yan, Y., Li, X., Zhang, C., Lv, L., Gao, B., and Li, M. (2021). Research Progress on Antibacterial Activities and Mechanisms of Natural Alkaloids: A Review. Antibiotics, 10.","DOI":"10.3390\/antibiotics10030318"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Naeem, A., Hu, P., Yang, M., Zhang, J., Liu, Y., Zhu, W., and Zheng, Q. (2022). Natural Products as Anticancer Agents: Current Status and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27238367"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"709","DOI":"10.4155\/fmc-2019-0016","article-title":"Phenanthridine Derivatives as Promising New Anticancer Agents: Synthesis, Biological Evaluation and Binding Studies","volume":"12","author":"Azad","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"147648","DOI":"10.1155\/2014\/147648","article-title":"Protein-Protein Interaction Detection: Methods and Analysis","volume":"2014","author":"Rao","year":"2014","journal-title":"Int. J. Proteom."},{"key":"ref_60","first-page":"1934578X241239169","article-title":"Network Pharmacology Approach and Partial Experimental Validation of Aidi Injection Solution for the Treatment of Colorectal Cancer","volume":"19","author":"Yu","year":"2024","journal-title":"Nat. Prod. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Peng, Y., Wang, Y., Zhou, C., Mei, W., and Zeng, C. (2022). PI3K\/Akt\/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.819128"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1177\/1947601912455199","article-title":"Dual Roles of MDM2 in the Regulation of P53","volume":"3","author":"Shi","year":"2012","journal-title":"Genes Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e470","DOI":"10.1002\/mco2.470","article-title":"Heat Shock Protein 90: Biological Functions, Diseases, and Therapeutic Targets","volume":"5","author":"Wei","year":"2024","journal-title":"MedComm"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112268","DOI":"10.1016\/j.ejmech.2020.112268","article-title":"Dihydrofolate Reductase Inhibitors for Use as Antimicrobial Agents","volume":"195","author":"He","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3109\/10409239109114072","article-title":"DNA Gyrase: Structure and Function","volume":"26","author":"Reece","year":"1991","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Valliammai, A., Selvaraj, A., Muthuramalingam, P., Priya, A., Ramesh, M., and Pandian, S.K. (2021). Staphyloxanthin Inhibitory Potential of Thymol Impairs Antioxidant Fitness, Enhances Neutrophil Mediated Killing and Alters Membrane Fluidity of Methicillin Resistant Staphylococcus aureus. Biomed. Pharmacother., 141.","DOI":"10.1016\/j.biopha.2021.111933"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/6\/434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:48:40Z","timestamp":1760032120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/6\/434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":66,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cimb47060434"],"URL":"https:\/\/doi.org\/10.3390\/cimb47060434","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]}}}