{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:00:27Z","timestamp":1784750427064,"version":"3.55.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["308590\/2017\u20131 309648\/2019\u20130 431254\/2018\u20134"],"award-info":[{"award-number":["308590\/2017\u20131 309648\/2019\u20130 431254\/2018\u20134"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>Parasitic diseases remain as unresolved health issues worldwide. While for some parasites the treatments involve drug combinations with serious side effects, for others, chemical therapies are inefficient due to the emergence of drug resistance. This urges the search for novel antiparasitic agents able to act through multiple mechanisms of action. Here, we report the first multi-target model based on quantitative structure-activity relationships and a multilayer perceptron neural network (mt-QSAR-MLP) to virtually design and predict versatile inhibitors of proteins involved in the survival and\/or infectivity of different pathogenic parasites. The mt-QSAR-MLP model exhibited high accuracy (&amp;gt;80%) in both training and test sets for the classification\/prediction of protein inhibitors. Several fragments were directly extracted from the physicochemical and structural interpretations of the molecular descriptors in the mt-QSAR-MLP model. Such interpretations enabled the generation of four molecules that were predicted as multi-target inhibitors against at least three of the five parasitic proteins reported here with two of the molecules being predicted to inhibit all the proteins. Docking calculations converged with the mt-QSAR-MLP model regarding the multi-target profile of the designed molecules. The designed molecules exhibited drug-like properties, complying with Lipinski\u2019s rule of five, as well as Ghose\u2019s filter and Veber\u2019s guidelines.<\/jats:p>","DOI":"10.3389\/fchem.2021.634663","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T04:48:12Z","timestamp":1615351692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["QSAR Modeling for Multi-Target Drug Discovery: Designing Simultaneous Inhibitors of Proteins in Diverse Pathogenic Parasites"],"prefix":"10.3389","volume":"9","author":[{"given":"Valeria V.","family":"Kleandrova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Jaime","family":"Bezerra Mendon\u00e7a Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Muratov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus T.","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Speck-Planche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1007\/s10393-019-01405-7","article-title":"The one health approach to toxoplasmosis: epidemiology, control, and prevention strategies","volume":"16","author":"Aguirre","year":"2019","journal-title":"EcoHealth"},{"key":"B2","doi-asserted-by":"publisher","first-page":"534","DOI":"10.3389\/fchem.2019.00534","article-title":"In silico guided drug repurposing: discovery of new competitive and non-competitive inhibitors of falcipain-2","volume":"7","author":"Alberca","year":"2019","journal-title":"Front. 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