Novel 2-substituted benzothiazole derivatives: synthesis, in vitro and in silico evaluations as potential anticancer agents

Abstract

Cancer remains a global health concern, demanding the development of new therapeutic medicines. This research focuses on the synthesis, in vitro evaluation, and in silico analysis of new 2-substituted benzothiazole derivatives as possible anticancer drugs. Hybrid molecules comprising benzothiazole and pyridinone rings 8a–c and 10a–c were also synthesized. Several compounds were produced and characterized, using NMR, IR and elemental analysis, with promising anticancer activity against lung H1299, liver Hepg2 and breast MCF7 cancer cell lines. Structure–activity connection investigations identified crucial structural characteristics that influence potency, with benzylidine derivatives 6a–g demonstrating higher activity. In silico ADME research revealed favorable drug-like features for chosen compounds, such as high gastrointestinal absorption and selective CYP inhibition. Toxicological projections indicated few side effects, confirming their potential as medication candidates. Inverse-docking analysis of the five potent compounds 6a–c, 6e, and 6f against 12 selected protein tyrosine kinases (PTKs) and cyclin-dependent kinases (CDKs) revealed good docking scores, strong interaction patterns, and potential inhibitory effects, particularly against ABL1, ABL2, CDK4, and CDK6 enzymes, suggesting these compounds as promising candidates for further drug development.