Ruthenium(II) polypyridyl complexes with 1,8-naphthalimide group as DNA binder, photonuclease, and dual inhibitors of topoisomerases I and IIα

Two ruthenium(II) polypyridyl complexes containing 1,8-naphthalimide group as DNA binders, photonucleases, and inhibitors of topoisomerases I and Il alpha are evaluated. The binding properties of [Ru(phen)(2)(pnip)](2+) {1; phen = 1,10-phenanthroline; pnip = 12-[N-(p-phenyl)-1,8-napthalimide]-imidazo[4',5'-f] [1,10]phenanthroline} and [Ru(bpy)(2)(pnip)](2+) (2; bpy = 2,2'-bipyridine) with calf thymus DNA increases with increasing the bulkiness and hydrophobic character of ancillary ligands, although the two complexes possess high affinities for DNA via intercalation. Moreover, photoirradiation (lambda = 365 nm) of the two complexes are found to induce strand cleavage of closed circular pBR322 plasmid DNA via singlet oxygen mechanism, while complex 1 displays more effective photocleavage activity than complex 2 under the same conditions. Topoisomerase inhibition and DNA strand passage assay reflect that complexes 1 and 2 are efficient dual poisons of topoisomerases I and H alpha. (C) 2016 Published by Elsevier Inc.