{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:18:48Z","timestamp":1790965128516,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Leishmaniasis, a disease caused by <jats:italic>Leishmania<\/jats:italic> parasites, poses a significant health threat globally, particularly in Latin America and Brazil. <jats:italic>Leishmania amazonensis<\/jats:italic> is an important species because it is associated with both cutaneous leishmaniasis and an atypical visceral form. Current treatments are hindered by toxicity, resistance, and high cost, driving the need for new therapeutic targets and drugs. N\u2010myristoyltransferase (NMT) is an important anti\u2010leishmanial target. N\u2010myristoyltransferase (NMT) is an important target in <jats:italic>Leishmania<\/jats:italic> parasites, as it plays a crucial role in the process of myristoylation, a lipid modification that involves the attachment of myristate, a 14\u2010carbon saturated fatty acid, to the N\u2010terminus of specific proteins. In this work, a shape\u2010based modeling approach was employed to identify potential NMT inhibitors in <jats:italic>Leishmania amazonensis<\/jats:italic>. Using a pyrazole sulphonamide as a reference ligand, a five\u2010feature shape\u2010based model was developed and validated. Virtual screening of the DIVERSet EXP and CL libraries (~1 million compounds) prioritized the top 500 ranked molecules per subset based on the TanimotoCombo score. Molecular docking studies identified the three highest\u2010ranking compounds from each subset based on ChemPLP scores and docking pose consistency. Among the selected ligands, CL 54016012, EXP 6689657, and EXP 9226834 exhibited the most favorable binding interactions, with CL 54016012 forming stable hydrogen bonds with Tyr80, Tyr217, and Tyr345. Molecular dynamics (MD) simulations indicated that ligand binding did not significantly alter NMT structural stability, although variations in binding energy and hydrogen bond were observed. CL 54016012 demonstrated the highest docking score, optimal RMSD stability, and the lowest predicted IC50 value (19.81\u2009\u03bcM), suggesting its potential as a lead compound. In\u00a0vitro cytotoxicity assays revealed that CL 54016012, CL 74995016, and EXP 6689657 reduced <jats:italic>L. amazonensis<\/jats:italic> viability in a dose\u2010dependent manner, placing them as promising candidates for further investigation in anti\u2010leishmanial drug development.<\/jats:p>","DOI":"10.1111\/cbdd.70170","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T08:31:17Z","timestamp":1757320277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation of Potential Inhibitors of N\u2010Myristoyltransferase in <i>Leishmania amazonensis<\/i>: A Computational and Experimental Study"],"prefix":"10.1111","volume":"106","author":[{"given":"Mariana","family":"Sant\u2019Anna Pereira Nicolau","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Millena Almeida","family":"Resende","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Modeling, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia","family":"de Campos Chaves","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Santos","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veridiana","family":"de Melo Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7148-5813","authenticated-orcid":false,"given":"Nilson","family":"Nicolau\u2010Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Modeling, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Aparecida Geraldo","family":"Yoneyama","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology Federal University of Uberlandia  Uberlandia MG 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