Indole-7-carbaldehyde thiosemicarbazone as a flexidentate ligand toward ZnII, CdII, PdII and PtII ions: cytotoxic and apoptosis-inducing properties of the PtII complex

Abstract

A new thiosemicarbazone (LH₂) derived from indole-7-carbaldehyde was synthesized and reacted with Zn^II, Cd^II, Pd^II and Pt^II salts. The reactions with zinc and cadmium salts in 2 : 1 (ligand–metal) molar ratio afforded complexes of the type MX₂(LH₂)₂, (X = Cl, Br or OAc), in which the thiosemicarbazone acts as a neutral S-monodentate ligand. In the presence of potassium hydroxide, the reaction of LH₂ with ZnBr₂ resulted in deprotonation of the thiosemicarbazone at the hydrazine and indole nitrogens to form Zn(L)(CH₃OH). The reaction of LH₂ with K₂PdCl₄ in the presence of triethylamine, afforded Pd(L)(LH₂) which contains two thiosemicarbazone ligands: one being dianionic N,N,S-tridentate while the other one is neutral S-monodentate. When PdCl₂(PPh₃)₂ was used as the Pd^II ion source, Pd(L)(PPh₃) was obtained. In a similar manner, the analogous platinum complex, Pt(L)(PPh₃), was synthesized. The thiosemicarbazone in the latter two complexes behaves in a dianionic N,N,S-tridentate fashion. The platinum complex was found to have significant cytotoxicity toward four cancer cells lines, namely MDA-MB-231, MCF-7, HT-29, and HCT-116 but not toward the normal liver WRL-68 cell line. The apoptosis-inducing properties of the Pt complex was explored through fluorescence microscopy visualization, DNA fragmentation analysis and propidium iodide flow cytometry.