Ruthenium(II)-arene complexes with naphthalimide-tagged N,O- and N,N-chelating ligands: Synthesis and biological evaluation

A new family of ruthenium(II)-arene complexes with naphthalimide functionalized N,O- and N,N-chelating ligands of the general formula [Ru(eta(6)-p-cymene)Cl(L)] (2b-4b) (where: L = 4-[N-(2-((2-hydroxy-5-Br-phenyl)methyl imino)ethyl)]-N-butyl-1,8-naphthalimide (2a), 4-[N-(2-((2-hydroxy-5-Cl-phenyl)methyl imino)ethyl)]-N-butyl-1,8-naphthalimide (3a), and N-butyl-4-[N-(2-((2-hydroxy-5-NO2-phenyl)methylimino)ethyl)]-N-butyl-1,8-naphthalimide (4a), and [Ru(eta(6)-p-cymene) Cl(L')]Cl (8b-9b) (where L' = N-(2,2'-dipyridylaminoethyl)-1,8-naphthalimide (8a) and N-(2,2'-dipyridylaminopropyl)-1,8- naphthalimide (9a) have been synthesized and characterized. The in vitro cytotoxic activities of the ligands (2a, 9a) and the complexes (2b-4b, and 8b-9b) have been evaluated against the human melanoma skin cancer (CRL7687) and normal noncancerous (CA-M75) cell lines. All the compounds exhibit potent cytotoxic activities with IC50 values of similar to 1 mu M or less but displayed variable selectivity. The compounds with N,O-ligands were found to be less selective than those containing N, N-chelating ligands. Notably, complex 9b displayed the highest selectivity towards cancer cells over health cells. The interactions of the compounds with calf thymus DNA (CT-DNA) have also been investigated by UV-Vis and fluorescence spectra, ethidium bromide displacement assay and gel electrophoretic studies, which revealed that the compounds bind to CT-DNA moderately presumably through an intercalative mode. (C) 2015 Elsevier B.V. All rights reserved.