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 ovanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, H-1 & C-13 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 CTDNA 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., MCF7 (breast), MIAPACA2 (pancreatic), HeLa (cervix) and HepG2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C30H20Cl2CuN5O7S2] complex, exhibited pronounced specific cytotoxicity with GI(50) value of 4.8g/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.