Enantiomeric fluoro-substituted benzothiazole Schiff base-valine Cu(II)/Zn(II) complexes as chemotherapeutic agents: DNA binding profile, cleavage activity, MTT assay and cell imaging studies

Abstract To evaluate the biological preference of chiral drugs toward DNA target, new metal-based chemotherapeutic agents of Cu(II) and Zn(II), l -/ d -fluorobenzothiazole Schiff base-valine complexes 1 & 2 ( a and b ), respectively were synthesized and thoroughly characterized. Preliminary in vitro DNA binding studies of ligand L and complexes 1 & 2 ( a and b ) were carried out in Tris–HCl buffer at pH 7.2 to demonstrate the chiral preference of l -enantiomeric complexes over the d -analogues. The extent of DNA binding propensity was ascertained quantitatively by K b , K and K sv values which revealed greater binding propensity by l -enantiomeric Cu(II) complex 1a and its potency to act as a chemotherapeutic agent. The cleavage studies with pBR322 plasmid DNA revealed higher nuclease activity of 1a as compared to 2a via hydrolytic cleavage mechanism. The complexes 1 & 2 ( a and b ) were also screened for antimicrobial activity which demonstrated significantly good activity for l -enantiomeric complexes. Furthermore, cytotoxicity of the complexes 1a and 1b was evaluated by the MTT assay on human HeLa cancer cell line which implicated that more than 50% cells were viable at 15 μM. These results were further validated by cell imaging studies which demonstrated the nuclear blebbing.