Novel polypyridyl ruthenium complexes acting as high affinity DNA intercalators, potent transcription inhibitors and antitumor reagents.

Novel polypyridyl ruthenium complexes acting as high affinity DNA intercalators, potent transcription inhibitors and antitumor reagents.
J Inorg Biochem. 2018 May 02;185:1-9
Authors: Ma GL, Bi XD, Gao F, Feng Z, Zhao DC, Lin FJ, Yan R, Liu D, Liu P, Chen J, Zhang H
Abstract
Six novel polypyridyl ruthenium complexes with (E)-2-styryl-1H- imidazo[4,5-f][1,10]phenanthroline ligand and its analogues have been designed to enhance the DNA intercalation ability of their model compound [Ru(bpy)2(pip)]2+ (bpy = 2,2'-bipyridine, pip = 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline). As shown in the optimized geometry of the complexes, the introduction of styryl group not only extended the conjugated area of the intercalative ligand, but also retained the excellent planarity. These two merits have been proven to be beneficial for their DNA intercalation, thus greatly improved their inhibition activity towards DNA transcription by RNA polymerase and DNA topoisomerase, two enzymes closely related to both DNA and tumor cell growth. The relationships between the substituent group structures and the biological activities have also been investigated from energetic and electronic aspects by quantum chemistry calculations. Results from cell cytotoxicity and apoptosis assay testified that the styryl substituted ruthenium complexes possessed higher antitumor activity than [Ru(bpy)2(pip)]2+, as expected. As quantified in the MTT (3-(4,5-dimethylth...

Source: Journal of Inorganic Biochemistry - May 2, 2018 Category: Biochemistry Authors: Ma GL, Bi XD, Gao F, Feng Z, Zhao DC, Lin FJ, Yan R, Liu D, Liu P, Chen J, Zhang H Tags: J Inorg Biochem Source Type: research