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

<p>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)<sub>3</sub>(bpy)L]X manganese containing CORMs [bpy = 2,2′-bipyridine, X = hexafluorophosphate (PF<sub>6</sub>), trifluoromethanesulfonate (OTf), L = imidazole, methylimidazole, benzimidazole, N-benzylbenzimidazole, N-(4-chlorobenzyl)benzimidazole] to release CO in human invasive ductal breast (MCF-7) cell line. <i>In vitro</i> 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.</p>