Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells.

A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4',4″-tri--butyl-2,2':6',2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl(terpy)] (), {-PtCl(NH)(-pyrazine)ZnCl(terpy)} (), {-PtCl(NH)(-pyrazine)ZnCl(terpy)} (), {-PtCl(NH)(-4,4'-bipyridyl)ZnCl(terpy)} () and {-PtCl(NH)(-4,4'-bipyridyl)ZnCl(terpy)} () (where terpy = 4,4',4″-tri--butyl-2,2':6',2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower and constant values compared to cisplatin analogs. The lowest value belonged to complex while exhibited the highest. Molecular docking studies reveal that the binding of complex to DNA is due to van der Waals forces, while that of - is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.