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-HC1 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 la and its potency to act as a chemotherapeutic agent. The cleavage studies with pBR322 plasmid DNA revealed higher nuclease activity of la as compared to 2a via hydrolytic cleavage mechanism. The complexes1 & 2 (a and b) were also screened for antimicrobial activity which demonstrated significantly good activity for L-enantiomeric complexes. Furthermore, cytotoxicity of the complexes la and lb was evaluated by the MIT assay on human HeLa cancer cell line which implicated that more than 50% cells were viable at 15 mu M. These results were further validated by cell imaging studies which demonstrated the nuclear blebbing. (C) 2015 Published by Elsevier B.V.