{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:46:43Z","timestamp":1761198403308,"version":"build-2065373602"},"reference-count":97,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T00:00:00Z","timestamp":1725753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005668","name":"Federal District Research Support Foundation (FAPDF)","doi-asserted-by":"publisher","award":["00193-00000869\/2021-31","306682\/2021-4"],"award-info":[{"award-number":["00193-00000869\/2021-31","306682\/2021-4"]}],"id":[{"id":"10.13039\/501100005668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development (CNPq)","doi-asserted-by":"publisher","award":["00193-00000869\/2021-31","306682\/2021-4"],"award-info":[{"award-number":["00193-00000869\/2021-31","306682\/2021-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidade de Bras\u00edlia (UnB)","award":["00193-00000869\/2021-31","306682\/2021-4"],"award-info":[{"award-number":["00193-00000869\/2021-31","306682\/2021-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Four afatinib derivatives were designed and modeled. These derivatives were compared to the known tyrosine-kinase inhibitors in treating Chronic Myeloid Leukemia, i.e., imatinib and ponatinib. The molecules were evaluated through computational methods, including docking studies, the non-covalent interaction index, Electron Localization and Fukui Functions, in silico ADMET analysis, QTAIM, and Heat Map analysis. The AFA(IV) candidate significantly increases the score value compared to afatinib. Furthermore, AFA(IV) was shown to be relatively similar to the ponatinib profile when evaluating a range of molecular descriptors. The addition of a methylpiperazine ring seems to be well distributed in the structure of afatinib when targeting the BCR-ABL enzyme, providing an important hydrogen bond interaction with the Asp381 residue of the DFG-switch of BCR-ABL active site residue and the AFA(IV) new chemical entities. Finally, in silico toxicity predictions show a favorable index, with some molecules presenting the loss of the irritant properties associated with afatinib in theoretical predictions.<\/jats:p>","DOI":"10.3390\/molecules29174254","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T04:15:01Z","timestamp":1725855301000},"page":"4254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Silico Molecular Modeling of Four New Afatinib Derived Molecules Targeting the Inhibition of the Mutated Form of BCR-ABL T315I"],"prefix":"10.3390","volume":"29","author":[{"given":"Kelvyn M. L.","family":"Rocha","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Health Sciences, University of Bras\u00edlia, Bras\u00edlia 70910-900, DF, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1365-177X","authenticated-orcid":false,"given":"\u00c9rica C. M.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Health Sciences, University of Bras\u00edlia, Bras\u00edlia 70910-900, DF, Brazil"},{"name":"Computational Chemistry Laboratory, Institute of Chemistry, University of Bras\u00edlia, Bras\u00edlia 70910-900, DF, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-5852","authenticated-orcid":false,"given":"Rafael C. C.","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Health Sciences, University of Bras\u00edlia, Bras\u00edlia 70910-900, DF, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8677-3239","authenticated-orcid":false,"given":"Jo\u00e3o B. L.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Health Sciences, University of Bras\u00edlia, Bras\u00edlia 70910-900, DF, Brazil"},{"name":"Computational Chemistry Laboratory, Institute of Chemistry, University of Bras\u00edlia, Bras\u00edlia 70910-900, DF, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Minciacchi, V.R., Kumar, R., and Krause, D.S. (2021). Chronic Myeloid Leukemia: A Model Disease of the Past, Present and Future. 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