{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:03Z","timestamp":1787029263091,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["MCTIC\/CNPq No.28\/2018"],"award-info":[{"award-number":["MCTIC\/CNPq No.28\/2018"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["No.409751\/2018-9"],"award-info":[{"award-number":["No.409751\/2018-9"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["CNPq 304158\/2019-4"],"award-info":[{"award-number":["CNPq 304158\/2019-4"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["CNPq 438712\/2018-8"],"award-info":[{"award-number":["CNPq 438712\/2018-8"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["No.2444225\/2018"],"award-info":[{"award-number":["No.2444225\/2018"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["APQ 02816-21"],"award-info":[{"award-number":["APQ 02816-21"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq), Brazil","award":["APQ-01577-17"],"award-info":[{"award-number":["APQ-01577-17"]}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["MCTIC\/CNPq No.28\/2018"],"award-info":[{"award-number":["MCTIC\/CNPq No.28\/2018"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["No.409751\/2018-9"],"award-info":[{"award-number":["No.409751\/2018-9"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["CNPq 304158\/2019-4"],"award-info":[{"award-number":["CNPq 304158\/2019-4"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["CNPq 438712\/2018-8"],"award-info":[{"award-number":["CNPq 438712\/2018-8"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["No.2444225\/2018"],"award-info":[{"award-number":["No.2444225\/2018"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["APQ 02816-21"],"award-info":[{"award-number":["APQ 02816-21"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa o Estado de Minas Gerais (FAPEMIG)","doi-asserted-by":"publisher","award":["APQ-01577-17"],"award-info":[{"award-number":["APQ-01577-17"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["MCTIC\/CNPq No.28\/2018"],"award-info":[{"award-number":["MCTIC\/CNPq No.28\/2018"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["No.409751\/2018-9"],"award-info":[{"award-number":["No.409751\/2018-9"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["CNPq 304158\/2019-4"],"award-info":[{"award-number":["CNPq 304158\/2019-4"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["CNPq 438712\/2018-8"],"award-info":[{"award-number":["CNPq 438712\/2018-8"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["No.2444225\/2018"],"award-info":[{"award-number":["No.2444225\/2018"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["APQ 02816-21"],"award-info":[{"award-number":["APQ 02816-21"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brasil (CAPES)-Finance Code 001","award":["APQ-01577-17"],"award-info":[{"award-number":["APQ-01577-17"]}]},{"name":"CAPES","award":["MCTIC\/CNPq No.28\/2018"],"award-info":[{"award-number":["MCTIC\/CNPq No.28\/2018"]}]},{"name":"CAPES","award":["No.409751\/2018-9"],"award-info":[{"award-number":["No.409751\/2018-9"]}]},{"name":"CAPES","award":["CNPq 304158\/2019-4"],"award-info":[{"award-number":["CNPq 304158\/2019-4"]}]},{"name":"CAPES","award":["CNPq 438712\/2018-8"],"award-info":[{"award-number":["CNPq 438712\/2018-8"]}]},{"name":"CAPES","award":["No.2444225\/2018"],"award-info":[{"award-number":["No.2444225\/2018"]}]},{"name":"CAPES","award":["APQ 02816-21"],"award-info":[{"award-number":["APQ 02816-21"]}]},{"name":"CAPES","award":["APQ-01577-17"],"award-info":[{"award-number":["APQ-01577-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Malaria, Chagas disease, and leishmaniasis are tropical diseases caused by protozoan parasites of the genera Plasmodium, Trypanosoma and Leishmania, respectively. These diseases constitute a major burden on public health in several regions worldwide, mainly affecting low-income populations in economically poor countries. Severe side effects of currently available drug treatments and the emergence of resistant parasites need to be addressed by the development of novel drug candidates. Natural 2,5-Diketopiperazines (2,5-DKPs) constitute N-heterocyclic secondary metabolites with a wide range of biological activities of medicinal interest. Its structural and physicochemical properties make the 2,5-DKP ring a versatile, peptide-like, and stable pharmacophore attractive for synthetic drug design. In the present work, twenty-three novel synthetic 2,5-DKPs, previously synthesized through the versatile Ugi multicomponent reaction, were assayed for their anti-protozoal activities against P. falciparum, T. cruzi, and L. infantum. Some of the 2,5-DKPs have shown promising activities against the target protozoans, with inhibitory concentrations (IC50) ranging from 5.4 to 9.5 \u00b5g\/mL. The most active compounds also show low cytotoxicity (CC50), affording selectivity indices \u2265 15. Results allowed for observing a clear relationship between the substitution pattern at the aromatic rings of the 2,5-DKPs and their corresponding anti-Plasmodium activity. Finally, calculated drug-like properties of the compounds revealed points for further structure optimization of promising drug candidates.<\/jats:p>","DOI":"10.3390\/ph17020223","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T09:00:02Z","timestamp":1707382802000},"page":"223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel 2,5-Diketopiperazines with In Vitro Activities against Protozoan Parasites of Tropical Diseases"],"prefix":"10.3390","volume":"17","author":[{"given":"Isabela P.","family":"Ceravolo","sequence":"first","affiliation":[{"name":"Laboratory of Immunopathology, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia F.","family":"Leoni","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoniana U.","family":"Krettli","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvane M. F.","family":"Murta","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics of Parasites, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-3022","authenticated-orcid":false,"given":"Daniela de M.","family":"Resende","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics of Parasites, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariza G. F. de M. L.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics of Parasites, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodieh O. S.","family":"Varej\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Product Chemistry Studies and Organic Synthesis, Federal University of Vi\u00e7osa (UFV), Av. PH Rolfs, s\/n, Vi\u00e7osa 36570-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena L.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Product Chemistry Studies and Organic Synthesis, Federal University of Vi\u00e7osa (UFV), Av. PH Rolfs, s\/n, Vi\u00e7osa 36570-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo V. V.","family":"Varej\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Product Chemistry Studies and Organic Synthesis, Federal University of Vi\u00e7osa (UFV), Av. PH Rolfs, s\/n, Vi\u00e7osa 36570-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5982-6083","authenticated-orcid":false,"given":"Markus","family":"Kohlhoff","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Natural Product Chemistry, Ren\u00e9 Rachou Institute (IRR), Oswaldo Cruz Foundation (FIOCRUZ), Av. Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2023, July 19). World Malaria Report 2022. Available online: Https:\/\/www.who.int\/Publications\/i\/Item\/9789240064898."},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2023, July 19). Chagas Disease. Available online: https:\/\/www.who.int\/News-Room\/Fact-Sheets\/Detail\/Chagas-Disease-(American-Trypanosomiasis)."},{"key":"ref_3","unstructured":"World Health Organization (WHO) (2023, July 19). Leishmaniasis. Available online: Https:\/\/www.who.int\/News-Room\/Fact-Sheets\/Detail\/Leishmaniasis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ijpddr.2019.11.004","article-title":"Current Trends in the Pharmacological Management of Chagas Disease","volume":"12","author":"Ribeiro","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106846","DOI":"10.1016\/j.actatropica.2023.106846","article-title":"A Review on New Natural and Synthetic Anti-Leishmanial Chemotherapeutic Agents and Current Perspective of Treatment Approaches","volume":"240","author":"Majumder","year":"2023","journal-title":"Acta Trop."},{"key":"ref_6","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_7","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_8","doi-asserted-by":"crossref","unstructured":"Song, Z., Hou, Y., Yang, Q., Li, X., Wu, S., Wang, C.-Y., and Wang, B.-G. (2021). Marine Drugs Structures and Biological Activities of Diketopiperazines from Marine Organisms: A Review. Mar. Drugs, 19.","DOI":"10.3390\/md19080403"},{"key":"ref_9","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_10","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_11","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1007\/s00044-012-0355-9","article-title":"The Cytotoxic Effects of Diketopiperaizes against Leishmania donovani Promastigotes and Amastigotes","volume":"22","author":"Maity","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_12","first-page":"562","article-title":"Diketopiperazine Alkaloids Produced by the Endophytic Fungus Penicillium Citrinum and Evaluation of Their Antileishmanial Activity","volume":"13","author":"Cruz","year":"2019","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bmc.2013.01.027","article-title":"\u03b1-Selective Glycosylation Affords Mucin-Related GalNAc Amino Acids and Diketopiperazines Active on Trypanosoma cruzi","volume":"21","author":"Campo","year":"2013","journal-title":"Bioorg Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1016\/j.bmc.2010.02.034","article-title":"Assessing the Trypanocidal Potential of Natural and Semi-Synthetic Diketopiperazines from Two Deep Water Marine-Derived Fungi","volume":"18","author":"Watts","year":"2010","journal-title":"Bioorg Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41429-020-00390-2","article-title":"Diatretol, an \u03b1, A\u2032-Dioxo-Diketopiperazine, Is a Potent In Vitro and In Vivo Antimalarial","volume":"74","author":"Ishiyama","year":"2021","journal-title":"J. Antibiot."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7048","DOI":"10.1016\/j.bmcl.2012.09.094","article-title":"Linear and Cyclic Dipeptides with Antimalarial Activity","volume":"22","author":"Olivo","year":"2012","journal-title":"Bioorg Med. Chem. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/anie.196200081","article-title":"The \u03b1-Addition of Immonium Ions and Anions to Isonitriles Accompanied by Secondary Reactions","volume":"1","author":"Ugi","year":"1962","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1021\/acs.jafc.1c07790","article-title":"2,5-Diketopiperazines via Intramolecular N-Alkylation of Ugi Adducts: A Contribution to the Synthesis, Density Functional Theory Study, X-ray Characterization, and Potential Herbicide Application","volume":"70","author":"Mendes","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/bs.podrm.2020.07.005","article-title":"Validation of In Vitro Bioassay Methods: Application in Herbal Drug Research","volume":"46","author":"Indrayanto","year":"2021","journal-title":"Profiles Drug Subst. Excip. Relat. Methodol."},{"key":"ref_20","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. Devel. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5893","DOI":"10.1016\/j.tetlet.2016.11.071","article-title":"Naseseazine C, a New Anti-Plasmodial Dimeric Diketopiperazine from a Marine Sediment Derived Streptomyces Sp.","volume":"57","author":"Buedenbender","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17320","DOI":"10.1021\/ja308429f","article-title":"Synthesis and Biological Evaluation of Epidithio-, Epitetrathio-, and Bis-(Methylthio)Diketopiperazines: Synthetic Methodology, Enantioselective Total Synthesis of Epicoccin G, 8,8\u2032-Epi-Ent-Rostratin B, Gliotoxin, Gliotoxin G, Emethallicin E, and Haematocin and Discovery of New Antiviral and Antimalarial Agents","volume":"134","author":"Nicolaou","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"647","DOI":"10.7164\/antibiotics.56.647","article-title":"New Diketopiperazines from the Entomopathogenic Fungus Verticillium Hemipterigenum BCC 1449","volume":"56","author":"Nilanonta","year":"2003","journal-title":"J. Antibiot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1002\/jlac.199619961123","article-title":"Structure Elucidation of Diatretol\u2014A New Diketopiperazine Metabolite from the Fungus Clitocybe diatreta","volume":"1996","author":"Arnone","year":"1996","journal-title":"Liebigs Ann. Chem"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15289","DOI":"10.1016\/j.tetlet.2021.152895","article-title":"Unified Enantioselective Total Synthesis of 3,6-Dioxygenated Diketopiperazine Natural Products, Diatretol and Lepistamides A, B and C","volume":"67","author":"Takahashi","year":"2021","journal-title":"Tetrahedron Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102267","DOI":"10.1016\/j.parint.2020.102267","article-title":"Metacytofilin Has Potent Anti-Malarial Activity","volume":"81","author":"Leesombun","year":"2021","journal-title":"Parasitol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s10482-020-01398-2","article-title":"Diketopiperazines and Other Bioactive Compounds from Bacterial Symbionts of Marine Sponges","volume":"113","author":"Santos","year":"2020","journal-title":"Antonie Leeuwenhoek"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2012.09.019","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"64","author":"Lipinski","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1002\/(SICI)1521-3773(19991216)38:24<3743::AID-ANIE3743>3.0.CO;2-U","article-title":"The Design of Leadlike Combinatorial Libraries","volume":"38","author":"Teague","year":"1999","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_31","first-page":"1","article-title":"Synthesis and Antiplasmodial Activity of 2-Methyl-3-Carboxyl-Naphtho [2,3-b] Furan Quinone Derivatives","volume":"1","author":"Siqueira","year":"2018","journal-title":"J. Med. Chem. Drug Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/0014-4894(88)90082-3","article-title":"Plasmodium Falciparum: Induction of Resistance to Mefloquine in Cloned Strains by Continuous Drug Exposure In Vitro","volume":"67","author":"Oduola","year":"1988","journal-title":"Exp. Parasitol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human Malaria Parasites in Continuous Culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1128\/AAC.48.5.1803-1806.2004","article-title":"Simple and Inexpensive Fluorescence-Based Technique for High-Throughput Antimalarial Drug Screening","volume":"48","author":"Smilkstein","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1186\/s12936-018-2568-y","article-title":"Aspidosperma Pyrifolium, a Medicinal Plant from the Brazilian Caatinga, Displays a High Antiplasmodial Activity and Low Cytotoxicity","volume":"17","author":"Ceravolo","year":"2018","journal-title":"Malar. J."},{"key":"ref_36","first-page":"21","article-title":"Actividad Antiparasitaria In Vitro de Plantas de La Medicina Tra-Dicional Tacana Sobre Plas-modium Faciparum a Trav\u00e9s Del M\u00e9todo Fluorom\u00e9trico-SYBR GreenI","volume":"8","author":"Condo","year":"2020","journal-title":"Con-Cienc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0887-2333(88)90030-6","article-title":"Comparisons of Two in Vitro Cytotoxicity Assays\u2014The Neutral Red (NR) and Tetrazolium MTT Tests","volume":"2","author":"Borenfreund","year":"1988","journal-title":"Toxicol. Vitr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0378-8741(02)00005-3","article-title":"Antimalarial Activity of Medicinal Plants Used in Traditional Medicine in S. Tom\u00e9 and Pr\u00edncipe Islands","volume":"81","author":"Gomes","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1078\/094471103322331458","article-title":"Cytotoxic Activity of Some Lichen Extracts on Murine and Human Cancer Cell Lines","volume":"10","author":"Tomasi","year":"2003","journal-title":"Phytomedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1590\/S0074-02762010000200022","article-title":"In Vitro and In Vivo Experimental Models for Drug Screening and Development for Chagas Disease","volume":"105","author":"Romanha","year":"2010","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1128\/AAC.40.11.2592","article-title":"Efficient Technique for Screening Drugs for Activity against Trypanosoma cruzi Using Parasites Expressing-Galactosidase","volume":"40","author":"Buckner","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","unstructured":"De Moura Lodi Cruz, M.G.F., Murta Santi, A.M., De Morais-Teixeira, E., Portes Caldeira, A.S., Pessoa de Sequeira, E., Oliveira, E., De Almeida Alves, T.M., and Fonseca Murta, S.M. (2023). Anti-Leishmania Compounds Can Be Screened Using Leishmania Spp. Expressing Red Fluorescence (tdTomato). Antimicrob. Agents Chemother., e00509-23. in press."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/2\/223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:57:06Z","timestamp":1760104626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/2\/223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ph17020223"],"URL":"https:\/\/doi.org\/10.3390\/ph17020223","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]}}}