(Dipyrido[3,2-a:2′,3′-c]phenazine)(glycinato)copper(II) perchlorate: A novel DNA-intercalator with anti-proliferative activity against thyroid cancer cell lines

Abstract

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. A novel copper(II) heteroleptic complex of dipyrido[3,2-a:2′,3′-c]phenazine (dppz) and glycinato (gly) as chelating ancillary ligand, [Cu(dppz)(gly)]ClO 4 (1), was synthesized and characterized. X-ray crystallography revealed that the coordination geometry of the cationic [Cu(dppz)(gly)]+ unit is hexacoordinated and shows a distorted octahedral coordination geometry in the solid state, with the N,N and N,O chelating atoms of dppz and glycinato, respectively, in the square plane and in which the planar units are connected in a monodimensional polymeric array by the apical copper coordination of the second carboxylic oxygen atom. Biological assays showed that 1 exhibits a remarkable anti-proliferative activity against the two human anaplastic thyroid cancer cell lines 8505c (BrafV600E/V600E) and SW1736 (BrafWT/V600E), in a dose-and time-dependent manner. In details, the IC 50 after 48 h of drug exposure was 2.86±0.54 μM for SW1736 and 1.05±0.48 μM for 8505c. On the other hand, the IC 50 shown by cis-diamminedichloroplatinum(II) (cisplatin) against the same cell lines was 2.50±0.40 μM and 6.03±0.78 μM, respectively. Optical microscopy observations, after 48 h of treatment, showed morphological cell changes typical of apoptosis, confirmed by DNA ladder assays. DNA interaction studies, performed by UV absorption spectrophotometry, circular dichroism and viscosimetry, clearly showed that [Cu(dppz)(gly)]ClO 4 is a DNA-intercalator, with a DNA-binding constant, K b , of 2.1×10 6 M −1, suggesting that the mechanism of the cytotoxic activity can be related to its DNA-binding.

DNA‐Binding and Anticancer Activity of Pyrene‐Imidazolium Derivatives

“…In addition, the presence of aromatic planar groups is key to allow π‐π stacking interactions with the DNA nitrogen bases, occurring in intercalation or top stacking . Very often the two groups are present in one molecule: the aromatic ring can be positively charged, positively charged residues can be appended on side groups, or a positive charge is conferred by metal ions in complexes of aromatic ligands …”

Metal complexes of amino acids and peptides

“…[138][139][140][141][142][143][144][145][146][147] Several 3d metals have also been involved into the studies, and especially Cu(II) complexes have been considered as potential anticancer compounds and potential alternatives to cisplatin. This has been also valid for the past two ones.…”

One-pot synthesis of benzopyranophenazines using graphene oxide dichlorotriazine (GO-DCT) under microwave irradiations

“…Phenazines have a number of pharmacological activities including anti-tumor [1], antimycobacterial [2], anti-proliferative, [3] antibiotics [4], antifungal [5], and anti-in ammatory [6]. Some phenazines isolated from Streptomyces (a marine bacterium) are described with biological signi cance ( Figure 1) [7][8][9][10].…”