New binuclear Ni(II) metallates as potent antiproliferative agents against MCF-7 and HeLa cells

Abstract

Four new binuclear nickel(II) metallates 1–4 were synthesized from the reaction between NiCl2·6H2O, 1,3-bis(diphenylphosphino)propane and [H2-(MSal-Rtsc)], where R=H, CH3, C2H5, C6H5, MSal=3-methoxysalicylaldehyde, tsc=thiosemicarbazone. The complexes were characterized by various spectral and analytical methods. Distorted square planar geometry of complexes 3 and 4 were evidenced from their crystal structures. Their binding interaction with calf-thymus DNA (CT DNA) and albumin (Bovine serum albumin) were analyzed with absorption and emission spectral titration studies. Based on the observations, the complexes 1–4 act as strong binders to CT-DNA and BSA. The antioxidant properties of the compounds were evaluated to test their free radical scavenging ability. All the complexes exhibited better antioxidant activity than the ligands and were found to be greater than that of the conventional standard vitamin C. Cell proliferation MTT assays performed for all the compounds in the human breast cancer (MCF-7) and human cervical cancer cell line (HeLa) exposed a significant growth inhibition. The complexes showed remarkably high cytotoxicity against human cervical cancer cells (HeLa) and human breast cancer cells (MCF-7) than the standard cisplatin. Among the four complexes, complex 3 was the most effective against MCF-7 (IC50 value of 4µM) and HeLa (2.33µM) compared with the other complexes 1 (8.51µM; 10.02µM), 2 (6.25µM; 2.40µM) and 4 (6.62µM; 4.33µM) respectively. Furthermore, the compounds resulted in ROS (reactive oxygen species)-mediated apoptosis, as indicated by DCFDA (2′,7′-dichlorodihydro-fluorescein diacetate) and sub-G1 DNA content was measured by fluorescent activated cell sorting (FACS) analysis.