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

Abstract

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)(NO)](MeOH) (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)(NO)], (1) has a distorted 6-coordinated octahedrally-based geometry, with a planar-based [CuNO] 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 CuCl 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.

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

“…They exhibited strong charge-transfer bands near 335 and 355 nm, respectively and 1 displayed a d-d transition ~ 645 nm in DMSO (see SI for Figure S1 and S2 ). Further, 1 and 2 are considerably stable toward air and moisture for>24 h. The structures of 1 and 2 exhibited distorted square pyramidal geometry, which is similar to what the literature reported previously ( Khan et al, 2016 ) and the analytical data are found to be consistent with the proposed molecular formulae (Scheme in Fig. 1 ) .…”

“…The FT-IR spectra of 1 and 2 exhibited N-H bands at ~ 3400 cm −1 for the Hnor ligands. ( Calligaris and Carugo, 1996 ) described characteristics of tryp’s coordinated NH 2 bands around 3290 cm −1 and carboxylate (-O-C = O) bands ~ 1625 cm −1 , which showed a significant shift from the free tryp ~ 1660 cm −1 ( Khan et al, 2016 ). The anti-symmetric and symmetric -C = O stretching vibration shifted to lower frequencies that confirms the terminal coordination mode of carboxylate.…”

Photophysical properties of [(norharmane)Re(CO)3 (L)]+ complexes (L = bpy, phen or dppz). Redox behavior of the excited states and their interaction with Calf Thymus DNA

“…Also, these complexes were cytotoxic against different cell lines. [45][46] Recently, it was demonstrated that silver(I) complexes of nHo were light stable and also cytotoxic against different cell lines 47 . Moreover, the complexes used in this work were cytotoxic against A549 cells, 37 phototoxic against S. typhimurium and showed photosensitizing potential against plasmid DNA 48 .…”

Organometallic (η6‐p‐cymene)ruthenium(II) complexes with thiazolyl‐based organic twigs: En route towards targeted delivery via human serum albumin of the potential anticancer agents

“…The cytotoxicity of the molecules was analyzed with the help of an MTT assay following standard protocol [ 49 ] reported earlier by us. [ 50–54 ] Following, in brief, it has been described in the SI.…”