Abstract

Half-sandwich Ru(II) complexes containingnitro-substituted furoylthiourealigands, bearing the general formula [(& eta; (6)-p-cymene)RuCl2(L)] (1-6) and [(& eta; (6)-p-cymene)RuCl(L)(PPh3)](+) (7--12), have been synthesized and characterized.In contrast to the spectroscopic data which revealed monodentate coordinationof the ligands to the Ru(II) ion via a "S"atom, single crystal X-ray structures revealed an unusual bidentateN, S coordination with the metal center forming a four-membered ring.Interaction studies by absorption, emission, and viscosity measurementsrevealed intercalation of the Ru(II) complexes with calf thymus (CT)DNA. The complexes showed good interactions with bovine serum albumin(BSA) as well. Further, their cytotoxicity was explored exclusivelyagainst breast cancer cells, namely, MCF-7, T47-D, and MDA-MB-231,wherein all of the complexes were found to display more pronouncedactivity than their ligand counterparts. Complexes 7-12 bearing triphenylphosphine displayed significant cytotoxicity,among which complex 12 showed IC50 valuesof 0.6 & PLUSMN; 0.9, 0.1 & PLUSMN; 0.8, and 0.1 & PLUSMN; 0.2 & mu;M againstMCF-7, T47-D, and MDA-MB-231 cell lines, respectively. The most activecomplexes were tested for their mode of cell death through stainingassays, which confirmed apoptosis. The upregulation of apoptotic inducingand downregulation of apoptotic suppressing proteins as inferred fromthe western blot analysis also corroborated the apoptotic mode ofcell death. The active complexes effectively generated reactive oxygenspecies (ROS) in MDA-MB-231 cells as analyzed from the 2 & PRIME;,7 & PRIME;-dichlorofluoresceindiacetate (DCFH-DA) staining. Finally, in vivo studiesof the highly active complexes (6 and 12) were performed on the mice model. Histological analyses revealedthat treatment with these complexes at high doses of up to 8 mg/kgdid not induce any visible damage to the tested organs.