{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:12:34Z","timestamp":1780341154820,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Leishmaniasis is a neglected disease caused by parasites of the genus\n                    <jats:italic>Leishmania sp<\/jats:italic>\n                    . that causes approximately 1 million cases and 650,000 deaths annually worldwide. Its treatment has several limitations mainly due to high toxicity and clinical resistance, and the search for alternatives is highly desirable. The present work aimed to design new antileishmanial compounds through a virtual screening of a small in\u2010house library of pyrimidine compounds, never tested against\n                    <jats:italic>Leishmania<\/jats:italic>\n                    , using the active site of trypanothione reductase (TR) as a target model. The compounds showed favorable affinity with the amino acid residues of the active site of TR. Pyr 1\u20139 were synthesized and tested against\n                    <jats:italic>Leishmania amazonensis<\/jats:italic>\n                    strain. Four derivatives demonstrated activity against promastigote (IC\n                    <jats:sub>50<\/jats:sub>\n                    value between 11.23 and 91.5\u00a0\u00b5M) and three other compounds demonstrated discreet activity against amastigote, IC\n                    <jats:sub>50<\/jats:sub>\n                    value between 81.29 and 153.21\u00a0\u00b5M. Based on the results obtained in the screening, three new pyrimidines Pyr 10\u201312 were designed to optimize activity, cytotoxicity, and selectivity. Pyr 10 and Pyr 11 demonstrated good activity against promastigotes, with IC\n                    <jats:sub>50<\/jats:sub>\n                    of 11.38\u00a0\u00b1\u00a09.7 and 20.01\u00a0\u00b1\u00a013.55\u00a0\u00b5M, respectively, and improved cytotoxicity and selectivity. No activity was obtained against amastigotes. Thus, this study contributes important information for the development of new pyrimidines active against\n                    <jats:italic>Leishmania<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202402881","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T22:24:27Z","timestamp":1736979867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structure\u2010based Virtual Screening and Drug Design Development of Leishmanicidal Pyrimidines"],"prefix":"10.1002","volume":"22","author":[{"given":"Gerliny Bezerra","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences Federal University of Pernambuco\/UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9rick Caique","family":"Santos Costa","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Postgraduate Program in Biological Sciences Federal University of Pernambuco\/UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenaide","family":"Severina do Monte","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences Federal University of Pernambuco\/UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gleybson Correia","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences Federal University of Pernambuco\/UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerson Peter","family":"da Silva Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Nutrition Department, Vit\u00f3ria Academic Center Federal University of Pernambuco  Vitoria de Santo Antao Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Scotti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Health Sciences Center, Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB) Federal University of Paraiba  Joao Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Tullius Scotti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Health Sciences Center, Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB) Federal University of Paraiba  Joao Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Oliveira Silva","sequence":"additional","affiliation":[{"name":"Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Santana","family":"de Sousa Oliveira","sequence":"additional","affiliation":[{"name":"Department of Immunology, Aggeu Magalh\u00e3es Research Center, Oswaldo Cruz Foundation Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Policarpo","family":"Ademar Sales Junior","sequence":"additional","affiliation":[{"name":"Department of Immunology, Aggeu Magalh\u00e3es Research Center, Oswaldo Cruz Foundation Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria R\u00eago","family":"Alves Pereira","sequence":"additional","affiliation":[{"name":"Department of Immunology, Aggeu Magalh\u00e3es Research Center, Oswaldo Cruz Foundation Federal University of Pernambuco  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-6169","authenticated-orcid":false,"given":"Sebasti\u00e3o","family":"Jos\u00e9 de Melo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Postgraduate Program in Pharmaceutical Sciences Federal University of Pernambuco\/UFPE  Recife Brazil"},{"name":"Department of Biosciences, Postgraduate Program in Biological Sciences Federal University of Pernambuco\/UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1815584"},{"issue":"2","key":"e_1_2_9_3_1","first-page":"366","article-title":"Uso de Python para Detec\u00e7\u00e3o de Fake News sobre a COVID\u201019: Desafios e Possibilidades","volume":"16","author":"Ferreira\u2010Neto P. 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