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development of new treatments for neglected tropical diseases (NTDs) remains a major challenge in the 21st century. In most cases, the available drugs are obsolete and have limitations in terms of efficacy and safety. The situation becomes even more complex when considering the low number of new chemical entities (NCEs) currently in use in advanced clinical trials for most of these diseases. Natural products (NPs) are valuable sources of hits and lead compounds with privileged scaffolds for the discovery of new bioactive molecules. Considering the relevance of biodiversity for drug discovery, a chemoinformatics analysis was conducted on a compound dataset of NPs with anti-trypanosomatid activity reported in 497 research articles from 2019 to 2024. Structures corresponding to different metabolic classes were identified, including terpenoids, benzoic acids, benzenoids, steroids, alkaloids, phenylpropanoids, peptides, flavonoids, polyketides, lignans, cytochalasins, and naphthoquinones. This unique collection of NPs occupies regions of the chemical space with drug-like properties that are relevant to anti-trypanosomatid drug discovery. The gathered information greatly enhanced our understanding of biologically relevant chemical classes, structural features, and physicochemical properties. These results can be useful in guiding future medicinal chemistry efforts for the development of NP-inspired NCEs to treat NTDs caused by trypanosomatid parasites.<\/jats:p>","DOI":"10.3390\/biom14081033","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T06:07:35Z","timestamp":1724134055000},"page":"1033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neglected Tropical Diseases: A Chemoinformatics Approach for the Use of Biodiversity in Anti-Trypanosomatid Drug Discovery"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-183X","authenticated-orcid":false,"given":"Marilia","family":"Valli","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), Institute of Physics of Sao Carlos, University of Sao Paulo (USP), Av. Joao Dagnone, n\u00b0 1100, Sao Carlos 13563-120, SP, Brazil"},{"name":"School of Pharmaceutical Sciences of Ribeirao Preto (FCFRP), University of Sao Paulo (USP), Avenida Professor Doutor Zeferino Vaz, s\/n, Ribeirao Preto 14040-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago H.","family":"D\u00f6ring","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), Institute of Physics of Sao Carlos, University of Sao Paulo (USP), Av. Joao Dagnone, n\u00b0 1100, Sao Carlos 13563-120, SP, Brazil"},{"name":"Department of Exact Sciences and Education (CEE), School of Technology, Exact Sciences and Education (CTE), Federal University of Santa Catarina (UFSC), Blumenau 89036-256, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-9405","authenticated-orcid":false,"given":"Edgard","family":"Marx","sequence":"additional","affiliation":[{"name":"Agile Knowledge Engineering and Semantic Web (AKSW), Institute of Computer Science, Leipzig University of Applied Sciences (HTWK), 04109 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-0639","authenticated-orcid":false,"given":"Leonardo L. 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Available online: https:\/\/sustainabledevelopment.un.org\/content\/documents\/21252030%20Agenda%20for%20Sustainable%20Development%20web.pdf."},{"key":"ref_4","unstructured":"World Health Organization (2024, June 01). Global Report on Neglected Tropical Diseases. Available online: https:\/\/www.who.int\/teams\/control-of-neglected-tropical-diseases\/global-report-on-neglected-tropical-diseases-2024."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1016\/j.drudis.2022.04.004","article-title":"Approaches to advance drug discovery for neglected tropical Diseases","volume":"27","author":"Ferreira","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mukherjee, S. (2023). The United States Food and Drug Administration (FDA) regulatory response to combat neglected tropical diseases (NTDs): A review. PLoS Negl. Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0011010"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41579-022-00777-y","article-title":"Anti-trypanosomatid drug discovery: Progress and challenges","volume":"21","author":"Wyllie","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_8","unstructured":"World Health Organization (2024, June 01). Chagas Disease (Also Known as American Trypanosomiasis). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nambala, P., Mulindwa, J., Chammudzi, P., Senga, E., Lemelani, M., Zgambo, D., Matovu, E., MacLeod, A., and Musaya, J. (2022). Persistently High Incidences of Trypanosoma brucei rhodesiense Sleeping Sickness With Contrasting Focus-Dependent Clinical Phenotypes in Malawi. Front. Trop. Dis., 3.","DOI":"10.3389\/fitd.2022.824484"},{"key":"ref_10","unstructured":"Drugs for Neglected Diseases Initiative (2024, June 01). R&D Portfolio June 2023\u201412 Treatments Delivered. Available online: https:\/\/dndi.org\/wp-content\/uploads\/2023\/07\/DNDi-RD-Portfolio-June-2023.pdf."},{"key":"ref_11","first-page":"20180169","article-title":"\u201cDrug-likeness\u201d properties of natural compounds","volume":"4","author":"Nyongbela","year":"2019","journal-title":"Phys. Sci. Rev."},{"key":"ref_12","unstructured":"SciFinder-n (2024, June 01). Chemical Abstracts Service. Available online: https:\/\/www.cas.org\/solutions\/cas-scifinder-discovery-platform\/cas-scifinder-n?gad_source=1."},{"key":"ref_13","unstructured":"Clarivate (2024, June 01). Web of Science. Available online: https:\/\/www.webofscience.com\/wos\/woscc\/smart-search."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13321-016-0174-y","article-title":"ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy","volume":"8","author":"Djoumbou","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13321-018-0302-y","article-title":"Life beyond the Tanimoto coefficient: Similarity measures for interaction fingerprints","volume":"10","author":"Bajusz","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1021\/ci500588j","article-title":"DataWarrior: An Open-Source Program for Chemistry Aware Data Visualization and Analysis","volume":"55","author":"Sander","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1177\/172460080201700213","article-title":"Bravais-Pearson and Spearman correlation coefficients: Meaning, test of hypothesis and confidence interval","volume":"17","author":"Artusi","year":"2002","journal-title":"Int. J. Biol. Markers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cmdc.200700139","article-title":"Lessons Learnt from Assembling Screening Libraries for Drug Discovery for Neglected Diseases","volume":"3","author":"Brenk","year":"2008","journal-title":"ChemMedChem"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.drudis.2016.08.009","article-title":"The many roles of molecular complexity in drug discovery","volume":"22","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s43586-022-00184-w","article-title":"Principal component analysis","volume":"2","author":"Greenacre","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10333","DOI":"10.1021\/acs.jpca.9b04437","article-title":"Noise Reduction in Solid-State NMR Spectra Using Principal Component Analysis","volume":"123","author":"Kusaka","year":"2019","journal-title":"J. Phys. Chem. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12156","DOI":"10.1021\/acs.jmedchem.9b01813","article-title":"Integrating the Impact of Lipophilicity on Potency and Pharmacokinetic Parameters Enables the Use of Diverse Chemical Space during Small Molecule Drug Optimization","volume":"63","author":"Miller","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114925","DOI":"10.1016\/j.ejmech.2022.114925","article-title":"Hit-to-lead optimization of a 2-aminobenzimidazole series as new candidates for chagas disease","volume":"246","author":"Martinez","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.drudis.2022.01.017","article-title":"Discovery solubility measurement and assessment of small molecules with drug development in mind","volume":"27","author":"Barrett","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1021\/acs.jmedchem.2c01577","article-title":"Trends in Molecular Properties, Bioavailability, and Permeability across the Bayer Compound Collection","volume":"66","author":"Kuhnke","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1021\/ci300447c","article-title":"In silico prediction of aqueous solubility using simple QSPR models: The importance of phenol and phenol-like moieties","volume":"52","author":"Ali","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1021\/ci010132r","article-title":"Reoptimization of MDL Keys for Use in Drug Discovery","volume":"42","author":"Durant","year":"2002","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7675","DOI":"10.1021\/acsomega.1c06347","article-title":"Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents against Trypanosoma cruzi","volume":"7","author":"Bernatchez","year":"2022","journal-title":"ACS Omega"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chaudhuri, M., Singha, U.K., Vanderloop, B.H., Tripathi, A., and Nes, W.D. (2022). Steroidal Antimetabolites Protect Mice against Trypanosoma brucei. Molecules, 27.","DOI":"10.3390\/molecules27134088"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Amang \u00c0 Ngnoung, G.A., Sidjui, L.S., Leutcha, P.B., Nganso Ditchou, Y.O., Tchokouaha, L.R.Y., Herbette, G., Baghdikian, B., Kowa, T.K., Soh, D., and Kemzeu, R. (2023). Antileishmanial and Antiplasmodial Activities of Secondary Metabolites from the Root of Antrocaryon klaineanum Pierre (Anacardiaceae). Molecules, 28.","DOI":"10.3390\/molecules28062730"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Louren\u00e7o, E.M.G., Di I\u00f3rio, J.F., da Silva, F., Fialho, F.L.B., Monteiro, M.M., Beatriz, A., Perdomo, R.T., Barbosa, E.G., Oses, J.P., and de Arruda, C.C.P. (2023). Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis. Microorganisms, 11.","DOI":"10.3390\/microorganisms11010225"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/8\/1033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:39:25Z","timestamp":1760110765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/8\/1033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["biom14081033"],"URL":"https:\/\/doi.org\/10.3390\/biom14081033","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]}}}