Nickel and zinc complexes of testosterone N4-substituted thiosemicarbazone: Selective cytotoxicity towards human colorectal carcinoma cell line HCT 116 and their cell death mechanisms

• Published in: Journal of inorganic biochemistry Vol. 208; p. 111097
• Main Authors: Heng, Mok Piew, Sim, Kae Shin, Tan, Kong Wai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2020
• Subjects: DNA interactions; Intrinsic pathway; Steroidal metal complexes; Testosterone Schiff base; Topoisomerase I poison; Steroidal metal complexes; DNA interactions; Intrinsic pathway; Topoisomerase I poison; Testosterone Schiff base
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2020.111097

Two new Schiff base ligands (TE and TF) were prepared from conjugation of testosterone with 4-(4-ethylphenyl)-3-thiosemicarbazide and 4-(4-fluorophenyl)-3-thiosemicarbazide, respectively. Their nickel (NE and NF) and zinc (ZE and ZF) complexes were reported. X-ray crystallography revealed a distorted square planar geometry was adopted by NE. The compounds demonstrated excellent selectivity towards the colorectal carcinoma cell line HCT 116 despite their weak preferences towards the prostate cancer cell lines (PC-3 and LNCaP). Against HCT 116, all these compounds were able to arrest cell cycle at G0/G1 phase and induce apoptosis via mitochondria-dependent (TE, NE, and TF) and extrinsic apoptotic pathway (ZE, NF, and ZF). Moreover, only ZE was able to act as topoisomease I poison and halt its enzymatic reactions although all compounds presented excellent affinity towards DNA. Two testosterone thiosemicarbazone Schiff base ligands, and their nickel and zinc complexes were synthesized. They demonstrated excellent selectivity towards the colorectal carcinoma (HCT 116) cell line and arrest cell cycle at G0/G1 phase amid the apoptosis-inducing properties. [Display omitted] •Schiff base ligands of testosterone with 4-(4-ethylphenyl)-3-thiosemicarbazide and 4-(4-fluorophenyl)-3-thiosemicarbazide, and their metal complexes (nickel and zinc) were synthesized.•The cytotoxic compounds arrest cell cycle at G0/G1 phase and induce apoptosis.•Zinc complex ZE act as topoisomerase I poison and display outstanding preferences towards the colorectal carcinoma cell line HCT 116.