Folate-based binuclear Mn(II) chelates with 2,2’-bipyridine/1,10- phenanthroline as targeted anticancer agents for colon cancer cells

Abstract

Researchers have shown significant interest in the chemistry of mixed ligand transition metal chelates due to their diverse applications and bonding features. Herein, we have reported the synthesis of two new binuclear Mn(II) chelates with the composition of [Mn2(FA)(Bpy)2(H2O)2Cl2].7H2O (Chelate 1) and [Mn2(FA)(Phen)2(H2O)2Cl2].7H2O (Chelate 2) (where, FA = folate anion, Bpy = 2,2'-bipyridine, Phen = 1,10-phenanthroline). The folate anion acts as a bridging ligand to obtain the binuclear complexes with the suggested composition. The chelates have been characterized by using elemental analysis, spectroscopic (FTIR, UV-vis), EI-MS and TGA techniques. Further, the results from density functional theory (DFT) computations support well the suggested structures, which indicate the development of distorted octahedral geometries around each Mn(II) center for both binuclear complexes. The sulforhodamine B (SRB) assay was used to assess the cytotoxicity of the chelates against a series of folate receptor-positive and -negative cell lines. The prepared chelates exhibit significant cytotoxic effects against folate receptor-positive cell lines, with colon cancer HCT116 cells being the most affected. Furthermore, the anticancer mechanism of action on the HCT116 cell line was investigated by analyzing the wound healing, cell cycle profile, expression of pro-apoptotic and anti-apoptotic proteins, as well as examining the morphological changes in treated cells. The results provided compelling evidence of binuclear Mn(II) chelates-induced cellular and nuclear alterations.