DNA BINDING, IN VITRO CYTOTOXICITY AND ANTICANCER DRUG MECHANISM OF COPPER(II) COMPLEX CONTAINING PYRIDYL-TRIAZINE LIGAND

Abstract

Mononuclear copper(II) complex [Cu(dppt)2(H2O)2](ClO4)2 (1), where dppt is bidentate NpyNtz donor asymmetric ligand (pyridyl-triazine) has been isolated. The X-ray crystal structure of 1 possesses a CuN4O2 chromophore with elongated octahedral geometry. The electronic and EPR spectral properties demonstrate that the solvent molecules strongly interacted in the axial position thereby weakens the CuN4 coordination plane. Absorption and emission spectral and electrochemical measurements clearly show the partial intercalative binding of 1 to calf thymus (CT) DNA. Remarkably, it exhibits potent cytotoxicity (IC50, 3.73 M) against human cervical carcinoma cells (HeLa), which is 4.5 times better than cisplatin and is non-toxic (IC50, >500 M) to normal mouse embryonic fibroblasts cells (NIH 3T3). It blocks cell cycle progression of HeLa cells in G1 phase. FACSverse analysis of 1 is suggestive of ROS (reactive oxygen species) generation and absolutely induces apoptotic cell death in HeLa cells.