Transition-metal norharmane compounds as possible cytotoxic agents: New insights based on a coordination chemistry...

New first-row transition-metal compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) are reported. The compounds have the general formula [M(LL)(Hnor)(NO₃)₂](MeOH)_0-1 (M=Co, Ni, Cu, Zn; LL=2,2'-bipyridyl (bpy), 1,10-phenanthroline (phen)) and have been characterized by physical and analytical methods. X-ray structural analysis revealed that the compound of formula [Cu(phen)(Hnor)(NO₃)₂], (1) has a distorted 6-coordinated octahedrally-based geometry, with a planar-based [CuN₃O] core, where Cu-L varies between 1.99 and 2.04Å and two weak axial CuO contacts (2.209 and 2.644Å) from two different nitrates. Based on spectroscopic similarities, the other compounds appear to have the same or very similar coordination geometries. The compounds showed clear cell growth inhibitory effects in two different cancer cell lines in vitro, with the copper and zinc complexes being the most toxic and in fact almost comparable to cisplatin. Flow-cytometry analysis confirmed induction of apoptosis in cancer cells treated with the compounds. Interestingly, co-incubation of the cells with metal complexes and CuCl₂ induced an increase in the cytotoxic effects, most likely due to the conversion of the metal compounds in the corresponding, and most active, copper analogues.