In Silico Molecular Modeling of Four New Afatinib Derived Molecules Targeting the Inhibition of the Mutated Form of BCR-ABL T315I.

ABSTRACT: 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

SUBMITTER: Rocha KML 

PROVIDER: S-EPMC11397288 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature