Platinum(ii/iv) complexes containing ethylenediamine-N,N′-di-2/3-propionate ester ligands induced caspase-dependent apoptosis in cisplatin-resistant colon cancer cells

Abstract

Several new R₂eddp (R = i-Pr, i-Bu; eddp = ethylenediamine-N,N′-di-3-propionate) esters and corresponding platinum(II) and platinum(IV) complexes of the general formula [PtCl_n(R₂edda-type)] (n = 2, 4) were synthesized and characterized by spectroscopic methods (IR, ¹H and ¹³C NMR) and elemental analysis. The crystal structure of platinum(IV) complex [PtCl₄{(c-Pe)₂eddip}] (3a) was resolved and is given herein. Ligand precursors, platinum(II), and platinum(IV) complexes were tested against eight tumor cell lines (CT26CL25, HTC116, SW620, PC3, LNCaP, U251, A375, and B16). Selectivity in the action of those compounds between tumor and two normal primary cells (fibroblasts and keratinocytes) are discussed. A structure–activity relationship of these compounds is discussed. Furthermore, cell cycle distribution, induction of necrosis, apoptosis, autophagy, anoikis, caspase activation, ROS, and RNS are presented on the cisplatin-resistant colon carcinoma HCT116 cell line.