New tailored substituted benzothiazole Schiff base Cu(II)/Zn(II) antitumor drug entities: effect of substituents on DNA binding profile,antimicrobial and cytotoxic activity

New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o?vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, ¹H & ¹³C NMR, ESI?MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C₃₀H₂₂CuN₅O₇S₂], [C₃₀H₂₀Cl₂CuN₅O₇S₂], [C₃₀H₂₀CuF₂N₅O₇S₂], [C₃₀H₂₂N₄O₄S₂Zn], [C₃₀H₂₀Cl₂N₄O₄S₂Zn], and [C₃₀H₂₀F₂N₅O₇S₂Zn], with CT?DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by K _b and K _sv values which gave higher binding propensity for chloro-substituted Cu(II) [C₃₀H₂₀Cl₂CuN₅O₇S₂] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski’s rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens viz., E. coli, S. aureus, P. aeruginosa, B. subtilis, and C. albicans. The cytotoxicity of the complexes [C₃₀H₂₀Cl₂CuN₅O₇S₂], [C₃₀H₂₀CuF₂N₅O₇S₂], [C₃₀H₂₀Cl₂N₄O₄S₂Zn], and [C₃₀H₂₀F₂N₅O₇S₂Zn] were evaluated against five human cancer cell lines viz., MCF?7 (breast), MIA?PA?CA?2 (pancreatic), HeLa (cervix) and Hep?G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C₃₀H₂₀Cl₂CuN₅O₇S₂] complex, exhibited pronounced specific cytotoxicity with GI₅₀ value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix.