Mitochondria-Dependent Apoptosis Inducer: Testosterone-N4-ethylthiosemicarbazonate and Its Metal Complexes with Selective Cytotoxicity Towards Human Colorectal Carcinoma Cell Line (HCT 116)

Abstract A Schiff base ligand (L) was prepared from the conjugation of testosterone with 4-ethyl-3-thiosemicarbazide and its nickel (C1) and zinc (C2) complexes were synthesized. Formation of these compounds were confirmed by 1H-NMR (for L), FTIR spectroscopy and elemental analysis. X-ray crystallography revealed that C1 adopted a distorted square planar geometry. The synthesized compounds were able to interact with DNA via intercalation (L) and surface binding (C1 and C2) with considerable affinity. Complexation with zinc rendered the steroidal compound (C2) inactive against all the cell lines tested but C1, along with its parent ligand (L), displayed selective cytotoxicity towards colorectal carcinoma cell line HCT 116 through mitochondria-dependent apoptosis and they were non-toxic to the normal colon cell line CCD-18Co. Moreover, selectivity index of these two compounds towards the colorectal carcinoma cell line tested was at least two fold better than that of cisplatin, thereby rendering them intriguing candidates for further studies