Mitochondria-dependent apoptosis inducer: Testosterone-N4-ethylthiosemicarbazonate and its metal complexes with selective cytotoxicity towards human colorectal carcinoma cell line (HCT 116)

A Schiff base ligand L was prepared from conjugation of testosterone with 4-ethyl-3-thiosemicarbazide and its nickel (C1) and zinc (C2) complex were synthesized. C2 was unable to inhibit the growth of all the cell line tested. However, its parent ligand L and its nickel counterpart C1 were able to induce mitochondria-dependent apoptosis and inhibit the growth of cancer cells while being relatively safe to the normal colon cell line tested. The former was proven to be a weak DNA binder while the latter has excellent affinity towards DNA. [Display omitted] •Nickel and zinc complexes of testosterone Schiff base were synthesized.•Compounds were characterized by spectroscopic methods and X-ray crystallography.•Compounds synthesized are selective towards colorectal carcinoma cell line HCT 116.•The cytotoxic compounds induce mitochondrial-dependent apoptosis in HCT 116 cell. 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.