Design, synthesis, and anticancer evaluation of benzothiazole–carboxamide hybrids: Insights from molecular docking and cell line studies

The synthesis and biological evaluation of benzothiazole–carboxamide hybrids (6a-6o) were systematically explored to develop potential anticancer agents. The hybrids were synthesized through a series of reactions: starting from 2-amino-5-fluorobenzenethiol, 2-chloromethyl-benzothiazole (3) was synthesized and further converted into (6-fluorobenzo[d]thiazol-2-yl) methanol (4) and subsequently oxidized to 6-fluorobenzo[d]thiazole-2-carboxylic acid (5). The final benzothiazole–carboxamide hybrids were obtained by coupling the carboxylic acid with various amines. Molecular docking studies against the protein targets 4WKQ and 6LUD revealed that compound 6b demonstrated superior binding affinity to 4WKQ, while compound 6j showed the best affinity for 6LUD. Substituents, particularly methyl and hydroxy groups, significantly affected binding interactions. Anticancer activity was assessed in MCF-7 (breast cancer), HCT-116 (colon cancer), and HEK-293 (normal human embryonic kidney) cell lines. Compound 6j (4-OH) was the most potent, with IC50 values of 6.56 μM in MCF-7 and 7.83 μM in HCT-116 cells, and showed lower toxicity in HEK-293 cells. These results highlight the promising potential of benzothiazole–carboxamide hybrids, particularly those with hydroxy and methyl substitutions, for further development as selective and potent anticancer agents.