Synthesis, structural characterization, molecular docking study, biological activity of carbon monoxide release molecules as potent antitumor agents.

Two series of carbon monoxide-releasing molecules (CORMs) containing cobalt 1 – 13 were synthesized, and their drug-like properties were preliminarily evaluated. This includes cytotoxicity, cell cycle, stability, mitochondrial induce, molecular docking, as well as western blotting and ADME properties. • Two series of CO-releasing molecules (CORMs) were designed and synthesized. • We evaluate their cytotoxicity of some CO-releasing molecules (CORMs). • Compound 1 demonstrated effective antitumour effect with an IC 50 value of 4.7 μM. • We investigate the antitumour effect of CO release of CORMs on HepG2 cells, Hela cells and MDA-MB231 cells. • Molecular docking study of compound 1. In this study, two series of novel carbon monoxide-releasing molecules (CO-RMs) containing Co were designed and synthesized. The synthesized complexes were characterized by IR, ESI-MS, 1H NMR and 13C NMR spectroscopies. The antitumor activity of all complexes on HepG2 cells, Hela cells and MDA-MB-231 cells were assayed by MTT. IC 50 values of complexes 1 – 13 were 4.7–548.6 µM. Among these complexes, complex 1 was presented with a high selectivity to HepG2 cells (IC 50 = 4.7 ± 0.76 μM). Compared with iCORM (inactive CORM), CORM (complex 1) showed a remarkable activity against tumor cells owing to co-effect of CO and the ligand of COX-2 inhibitor. In addition, complex 1 increased ROS in mitochondria and caused a decrease of dose-dependent mitochondrial membrane potential against HepG2 cells. Complex 1 down-regulated the expression of COX-2 protein in western blot analysis. The molecular docking study suggested that the complex 1 formed a hydrogen bond with amino acid R120 in the active site of the Human cyclooxygenase-2 (COX-2). Therefore, the complex 1 could induce apoptosis of HepG2 cells through targeting COX-2 and mitochondria pathways, and it maybe a potential therapeutic agent for cancer. [ABSTRACT FROM AUTHOR]