β-Carboline copper complex as a potential mitochondrial-targeted anticancer chemotherapeutic agent: Favorable attenuation of human breast cancer MCF7 cells via apoptosis

Abstract

The development of preferentially selective cancer chemotherapeutics is a new trend in drug research. Thus, we designed and synthesized novel ternary complexes, [Cu(tryp)(Hnor)2(DMSO)]NO3 (1) and [Zn(tryp)(Hnor)2(DMSO)]NO3 (2) (tryp = DL-Tryptophane; Hnor = Norharmane, β-carboline; DMSO = Dimethyl sulfoxide), characterized with elemental analysis, FTIR, UV–vis, FL, NMR, ESI-MS, and molar conductivity. Furthermore, the TD-DFT studies with UV–vis and FTIR validated the proposed structures of 1 and 2. Moreover, we evaluated the HOMO-LUMO energy gap and found that 1 has a smaller energy gap than 2. Then, 1 and 2 were assessed for anticancer chemotherapeutic potential against cancer cell lines MCF7 (human breast cancer) and HepG2 (human liver hepatocellular carcinoma) as well as the non-tumorigenic HEK293 (human embryonic kidney) cells. The MTT assay illustrated the preferentially cytotoxic behavior of 1 when compared with that of 2 and cisplatin (standard drug) against MCF7 cells. Moreover, 1 was exposed to MCF7 cells, and the results indicated the arrest of the G2/M phases, which followed the apoptotic pathway predominantly. Generation of ROS, GSH depletion, and elevation in LPO validated the redox changes prompted by 1. These studies establish the great potential of 1 as a candidate for anticancer therapeutics.

Keywords

• Copper complex
• Computational chemistry
• Anticancer
• MCF7
• Apotosis
• Cell cycle