Novel 3-benzylbenzo[d]thiazol-2(3H)-iminium salts as potent DNA benzylating agents: design, synthesis, MTT assay, and DFT calculation

New derivatives of 3-benzylbenzo[d]thiazol-2(3H)-iminium salt were developed, synthesized, and assessed for their cytotoxic effects on the MCF-7 cell line. Among them, two molecules, identified as 3g and 3i, demonstrated notable cytotoxic activity with IC50 values of 41.76 and 58.34 µmol/L respectively, compared to the reference drug Cis-platin, which has an IC50 of 22.36 ± 2.98 µmol/L. Subsequent DNA interaction docking studies were conducted with these compounds. The docking data revealed that both 3g and 3i effectively bind within the minor groove of DNA, showing a preference for interaction with AT-rich sequences over CG-rich sequences. These findings suggest that 3g and 3i are effective DNA-binding agents. Further analysis using Density Functional Theory (DFT) was performed to explore the potential of DNA benzylation by compound 3g. The DFT studies suggested that the benzylation of guanine bases by 3g could occur at room temperature. Nonetheless, further experimental investigations are necessary to validate this hypothesis. The DFT studies suggested that the benzylation of guanine bases by 3g could occur at room temperature. Nonetheless, further experimental investigations are necessary to validate this hypothesis.