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

Khan, Rais Ahmad, De Almeida, Andreia ORCID: https://orcid.org/0000-0002-6889-1503, Al-Farhan, Khalid, Alsalme, Ali, Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542, Ghazzali, Mohamed and Reedijk, Jan 2016. Transition-metal norharmane compounds as possible cytotoxic agents: new insights based on a coordination chemistry perspective. Journal of Inorganic Biochemistry 165 , pp. 128-135. 10.1016/j.jinorgbio.2016.07.001

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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)(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 2.04 Å and two weak axial Cusingle bondO contacts (2.209 and 2.644 Å) 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Uncontrolled Keywords:	Copper; Cobalt; Nickel; Zinc; 9H-Pyrido[3,4-b]indole; Antiproliferative properties
Publisher:	Elsevier
ISSN:	0162-0134
Date of First Compliant Deposit:	1 August 2016
Date of Acceptance:	7 July 2016
Last Modified:	08 Nov 2023 02:51
URI:	https://orca.cardiff.ac.uk/id/eprint/93457

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