title: Synthesis, characterization, DNA binding, DNA cleavage, protein binding and cytotoxic activities of Ru(II) complexes.
abstract: We report on the synthesis of novel Ru(II) compounds (Ru-1 to Ru-8) bearing R-pdc, 4-Cl-pbinh ligands (where R=4-CF3, 4-F, 4-OH pdc=3-phenyl-5-(1H-pyrrol-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide, pbinh=phenoxybenzylidene isonicotinyl hydrazides) and their in vitro antitumor activity toward the cell lines murine leukemia L1210, human lymphocyte CEM, human epithelial cervical carcinoma HeLa, BEL-7402 and Molt4/C8. Some of the complexes exhibited more potent antiproliferative activity against cell lines than the standard drug cisplatin. Ruthenium complex Ru-2 displayed potent cytotoxicity with than that of cisplatin. DNA-binding, DNA cleavage and protein binding properties of ruthenium complexes with these ligands are reported. Interactions of these ruthenium complexes with DNA revealed an intercalative mode of binding between them. Synchronous fluorescence spectra proved that the interaction of ruthenium complexes with bovine serum albumin (BSA) resulted in a conformational change of the latter.
authors.affiliation: National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz, Ministério da Saúde, Av. Brasil 4036, Prédio da Expansão, 8° Andar, Sala 814, Manguinhos, 21040-361 Rio de Janeiro, RJ, Brazil; Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: sthota@cdts.fiocruz.br.
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Thota
authors.affiliation: S. R. College of Pharmacy, Department of Pharmaceutical Chemistry & Toxicology, Ananthasagar, Warangal, Telangana 506371, India.
authors.forename: Srujana
authors.initials: S
authors.lastname: Vallala
authors.affiliation: S. R. College of Pharmacy, Department of Pharmaceutical Chemistry & Toxicology, Ananthasagar, Warangal, Telangana 506371, India.
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Yerra
authors.affiliation: Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Daniel Alencar
authors.initials: DA
authors.lastname: Rodrigues
authors.affiliation: National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz, Ministério da Saúde, Av. Brasil 4036, Prédio da Expansão, 8° Andar, Sala 814, Manguinhos, 21040-361 Rio de Janeiro, RJ, Brazil.
authors.forename: Nulgumnalli Manjunathaiah
authors.initials: NM
authors.lastname: Raghavendra
authors.affiliation: Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D053837:DNA Cleavage; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D012428:Ruthenium / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D008024:Ligands; D012710:Serum Albumin, Bovine; D012428:Ruthenium; D004247:DNA
keywords: Antiproliferative; Bovine serum albumin; DNA-binding; Ru(II) compounds