Potent Anti‐Cancer Activity of Benzo[ <i>d</i> ]Thiazole‐Isatin Conjugates: Induces S Phase Arrest and Cell Necrosis in A549 and HepG2 Cells

The search for new molecules in cancer therapeutics is essential for overcoming treatment limitations, targeting evolving cancer characteristics, minimizing side effects, and advancing scientific knowledge. In this context, a series of benzo[d]thiazole-isatin conjugates (6a-6m) has been synthesized successfully in three steps with excellent yields (>90%). The preliminary antiproliferative results demonstrate that these synthetic derivatives are comparable to the well-known tyrosine kinase inhibitor (TKI) sunitinib. Moreover, the evaluation of their cytotoxicity has revealed outstanding activity against various cancer cell lines, including A549, HePG2, MDA-MB-231, and SGC7901. This significant efficacy highlights their potential as effective anti-cancer agents. Mechanism of action (MoA) studies revealed that compound 6g arrests the A549 and HepG2 cells at S phase, and the compound 6g on HepG2 cells results in a large number of cell necroses. Binding affinity of 6g with EGFR and cyclin-dependent kinase 2 (CDK2) kinase gives better results than reference drugs gefitinib and roscovitine, respectively.