CO-releasing properties and anticancer activities of manganese complexes with imidazole/benzimidazole ligands

Abstract

Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the pathogenesis of cancer. CO is produced by enzymatic degradation of heme in mammals. Heme oxygenase 1 (HO-1) catalyzes the breakdown of heme into CO, ferrous iron, and biliverdin. CO induces HO-1 and inhibits cell proliferation. Cancer cells exposed to several stress factors (hypoxia, reactive oxygen species, cis-platin, and oxidative stress), and HO-1 displays cytoprotective role against oxidative stress and inhibits apoptosis, metastases, angiogenesis, and cell proliferation processes. Therefore, metal containing CO-releasing molecules (CORMs) have been designed as an effective cancer treatment strategy. CORMs are responsible for releasing controlled amounts of CO to cells and tissues. Thus, we synthesized [Mn(CO)3(bpy)L]X manganese containing CORMs [bpy = 2,2′-bipyridine, X = hexafluorophosphate (PF6), trifluoromethanesulfonate (OTf), L = imidazole, methylimidazole, benzimidazole, N-benzylbenzimidazole, N-(4-chlorobenzyl)benzimidazole] to release CO in human invasive ductal breast (MCF-7) cell line. In vitro experiments indicated that the compounds inhibited cell proliferation and exhibited cytotoxic effect on breast cancer cells. Moreover, side groups of the compounds enhanced the anticancer effects in MCF-7 cell line. These manganese containing CORMs gave promising results and may be used as a drug template for effective treatment of invasive ductal breast carcinoma.