New planar trans-copper(II) β-dithioester chelate complexes: synthesis, characterization, anticancer activity and DNA-binding/cleavage studies

Abstract

New planar trans-copper(II) β-dithioester complexes, [Cu(L)₂] (L = methyl-3-hydroxy-(3-pyridyl)-2-propenedithioate (L1 in 1), methyl-3-hydroxy-(2-naphthyl)-2-propenedithioate (L2 in 2), methyl-3-hydroxy-3-(p-methoxyphenyl)-2-propenedithioate (L3 in 3), methyl-3-hydroxy-3-(p-fluorophenyl)-2-propenedithioate (L4 in 4), and methyl-3-hydroxy-3-(p-bromophenyl)-2-propenedithioate (L5 in 5)), have been synthesized and characterized by elemental (C, H, N and S) analysis, ESI-MS, IR, and UV-vis spectra. The structures of HL3 and its corresponding complex 3 have been determined by X-ray crystallography. Electrochemical behavior of all complexes has been studied by cyclic voltammetry. All five planar complexes show efficient DNA-binding and DNA (PBR322)-cleavage in a concentration-dependent manner (1 > 3 > 5 > 2 > 4). Cleavage efficiency is enhanced in the presence of H₂O₂ as well as ascorbic acid. However, the order of increased efficiency of Cu(II) chelates differs in the presence of H₂O₂ as 4 > 1 > 2 > 3 > 5. Among these complexes, the pyridyl- and methoxy-functionalized 1 and 3 have shown higher self-activating capability in DNA-cleavage. All complexes show significant variation in IC₅₀ on MCF-7 cell line. Additionally, treatment with the complexes gradually increases apoptotic cell death in dose-dependent manner in RAW 264.7 cell line. These findings highlight potential cancer protective nature of these complexes.

Keywords:

• β-dithioester
• copper
• anticancer
• DNA binding

Acknowledgments

NS and MKY(SRF) acknowledge the financial support from the Council of Scientific and Industrial Research (CSIR, Project No. 01 (2679)/12/EMR-II) and Science and Engineering Research Board (SERB,SB/S1/IC-15/2014) New Delhi. The Department of Chemistry, CAS-UGC-I, Banaras Hindu University is acknowledged for the X-ray facility. MV is thankful to UGC, New Delhi, India for financial support; UGC-CAS programme to Department of Zoology for infrastructural facilities and AKM and GR (SRF) thank CSIR, New Delhi, India.