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The compounds significantly reduced haeme crystallization, with IC50 values &lt; 10 \u00b5M. The values were comparable to chloroquine\u2019s, with an IC50 of 1.50 \u00b1 0.01 \u00b5M. The compounds 4c and 4e prolonged the average survival time of the infected mice to 16.7 \u00b1 2.16 and 14.4 \u00b1 1.20 days, respectively. We also studied the effect of the compounds 4b, 4c, and 4e on another important human parasite, Leishmania mexicana, which is responsible for cutaneous leishmaniasis, demonstrating a potential leishmanicidal effect against promasigotes, with an IC50 &lt; 10 \u00b5M. Concerning the possible mechanism of action of these compounds on Lesihmania mexicana, we performed experiments demonstrating that these three compounds could induce the collapse of the parasite mitochondrial electrochemical membrane potential (\u0394\u03c6). The in vitro cytotoxicity assays against mammalian cancerous and noncancerous human cell lines showed that the studied compounds exhibit low cytotoxic effects. The ADME\/Tox analysis predicted moderate lipophilicity values, low unbound fraction values, and a poor distribution for these compounds. Therefore, moderate bioavailability was expected. We calculated other molecular descriptors, such as the topological polar surface area, according to Veber\u2019s rules, and except for 2 and 4i, the rest of the compounds violated this descriptor, demonstrating the low antimalarial activity of our compounds in vivo.<\/jats:p>","DOI":"10.3390\/ph16121709","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T03:25:31Z","timestamp":1702265131000},"page":"1709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, Antimalarial, Antileishmanial, and Cytotoxicity Activities and Preliminary In Silico ADMET Studies of 2-(7-Chloroquinolin-4-ylamino)ethyl Benzoate Derivatives"],"prefix":"10.3390","volume":"16","author":[{"given":"Joyce E.","family":"Guti\u00e9rrez","sequence":"first","affiliation":[{"name":"Organic Synthesis Laboratory, Faculty of Pharmacy, Central University of Venezuela, Los Chaguaramos 1041-A, Caracas 1040, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1916-6118","authenticated-orcid":false,"given":"Hegira","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud y Desarrollo Humano, Univesidad Ecotec, Km. 13.5 Samborond\u00f3n, Guayas, Guayaquil 092302, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Fernandez-Moreira","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Universidad Esp\u00edritu Santo, Samborond\u00f3n, Guayas, Guayaquil 092301, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Unidad de Bioqu\u00edmica, Facultad de Farmacia, Central University of Venezuela, Los Chaguaramos 1041-A, Caracas 1040, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0055-2804","authenticated-orcid":false,"given":"Michael R.","family":"Mijares","sequence":"additional","affiliation":[{"name":"Biotechnology Unit, Faculty of Pharmacy, Central University of Venezuela, Los Chaguaramos 1041-A, Caracas 1040, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5480-4608","authenticated-orcid":false,"given":"Juan Bautista","family":"De Sanctis","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hn\u011bvot\u00ednsk\u00e1 1333\/5, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u0148a","family":"Gursk\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky 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