Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

Abstract

A series of mono- and bi-metallic metal complexes (with Cu(II), Pt(II) and Zn(II)) with substituted polypyridyl ligands have been prepared and their binding affinities towards quadruplex (c-Myc and human telomeric) and duplex DNA (ds26 and calf thymus) determined using fluorescent indicator displacement (FID) assays and UV/vis spectroscopic titrations. These studies have shown that the number of aromatic rings and number/position of cyclic amine substituents on the ligands, play an important role in defining the DNA binding abilities of the resulting metal complexes. We also show that bi-metallic complexes prepared using a novel terpyridine-cyclen ligand have higher affinity towards G-quadruplex DNA as compared to their mono-metallic counterparts. Cytotoxicity assays were carried out for all the new complexes against an osteosarcoma cancer cell line (U2OS) as well as a normal fibroblast cell line (GM05757). Several of these compounds displayed cytotoxicity similar to that of cisplatin.

Downregulation of oncogenic RAS and c-Myc expression in MOLT-4 leukaemia cells by a salicylaldehyde semicarbazone copper(II) complex

“…Results showed much higher intake of copper ion (308 ng copper/mg of protein) without any adverse effect (MTT IC 50 (24 h)  > 125 μM) on MOLT-4 cells. The cellular uptake values are higher than those obtained for osmium(II)14 and platinum(II) complexes15 (2–3 ng /mg of protein after 24 h treatment in A2780 ovarian carcinomas and U2OS osteosarcomas respectively) previously reported.…”

Anthracene-terpyridine metal complexes as new G-quadruplex DNA binders

“…This difference was accounted by the square pyramidal coordination geometry of the Cu(II) complex that might hinder intercalation between two pairs of duplex DNA, unlike the square planar Pt(II) congener that has the propensity to act as a DNA intercalator [34]. Similar results were obtained by Vilar et al with a different set of copper(II) and platinum(II) terpyridine complexes [36,39,40].…”

“…As reported by Teulade-Fichou et al [35], this type of strategy was successfully applied for macrocyclic organic compounds of the bis-intercalator or tris-intercalator type. This success inspired us to explore a similar approach to improve the quadruplexselectivity of M(II)-terpyridine (M = Cu, Pt) complexes, known to interact with G-quadruplex sequences [34,[36][37][38][39][40], by combining these terpyridine metal cores with a planar intercalating anthracenyl group.…”

Cobalt(iii)porphyrin to target G-quadruplex DNA

“…[6][7][8][9] Most of the G-quadruplex ligands with extended π-systems interact by π-stacking interaction with the external guanine quartet of quadruplex DNA structures. 13,[20][21][22][23][24][25][26][27][28][29] They also interact by external π-stacking provided they afford a planar face or a large aromatic ancillary ligand. [17][18][19] Among the compounds able to target quadruplexes a number of metal complexes endowed with aromatic ligands were reported.…”