Thota Sreekanth, Vallala Srujana, Yerra Rajeshwar, Rodrigues Daniel Alencar, Raghavendra Nulgumnalli Manjunathaiah, Barreiro Eliezer J
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.
S. R. College of Pharmacy, Department of Pharmaceutical Chemistry & Toxicology, Ananthasagar, Warangal, Telangana 506371, India.
Int J Biol Macromol. 2016 Jan;82:663-70. doi: 10.1016/j.ijbiomac.2015.09.045. Epub 2015 Sep 28.
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.
我们报道了新型钌（II）化合物（Ru-1至Ru-8）的合成，这些化合物带有R-pdc、4-Cl-pbinh配体（其中R = 4-CF3、4-F、4-OH，pdc = 3-苯基-5-（1H-吡咯-2-基）-4,5-二氢-1H-吡唑-1-碳硫酰胺，pbinh = 苯氧基亚苄基异烟酰肼），以及它们对小鼠白血病L1210、人淋巴细胞CEM、人上皮宫颈癌HeLa、BEL-7402和Molt4/C8细胞系的体外抗肿瘤活性。一些配合物对细胞系表现出比标准药物顺铂更强的抗增殖活性。钌配合物Ru-2表现出比顺铂更强的细胞毒性。报道了这些配体的钌配合物的DNA结合、DNA切割和蛋白质结合特性。这些钌配合物与DNA的相互作用揭示了它们之间的插入结合模式。同步荧光光谱证明钌配合物与牛血清白蛋白（BSA）的相互作用导致后者的构象变化。
