Novel 2-Substituted Benzothiazole Derivatives: Synthesis, In-vitro and In- silico Evaluations as Potential Anticancer Agents

Abstract

<title>Abstract</title> Cancer remains a global health concern, demanding the development of new therapeutic medicines. This research focuses on the synthesis, <italic>in vitro</italic> evaluation, and <italic>in silico</italic> analysis of new 2-substituted benzothiazole derivatives as possible anticancer drugs. Hybrid molecules comprising benzothiazole and pyridinone rings <bold>10a-d</bold> and <bold>14a-d</bold> 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 particular benzylidine derivatives <bold>7a-g</bold> demonstrating higher activity. <italic>In-silico</italic> 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. Docking studies revealed their binding mechanisms and interactions with protein tyrosine kinases PTK, identifying intriguing candidates for further study.