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

• New enantiomeric Cu(II)/Zn(II) complexes, 1 & 2 (a and b) derived from flurobenzothiazole Schiff base ligand were synthesized.
• Preliminary in vitro DNA binding studies with CT DNA revealed highest DNA binding propensity of l-enantiomeric Cu(II) complex 1a.
• Complex 1a and b cleaved pBR322 DNA via hydrolytic pathway with significantly good activity shown by l-enantiomeric complex.
• Cytotoxic results of complexes 1a and b against HeLa cancer line implicated that more than 50% cells were viable at 15 μM.

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 Kb, K and Ksv 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 2avia 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.

MTT assay and molecular docked model of enantiomeric l-fluoro benzothiazole Schiff base-valine Cu(II) complex, 1 (a).Figure optionsDownload as PowerPoint slide