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钌(II)多吡啶配合物的合成、表征、DNA结合及抗肿瘤活性

Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes.

作者信息

Srishailam A, Gabra Nazar Mohammed, Kumar Yata Praveen, Reddy Kotha Laxma, Devi C Shobha, Anil Kumar D, Singh Surya S, Satyanarayana S

机构信息

Department of Chemistry, Osmania University, Hyderabad 500007, India.

Department of Biochemistry, Osmania University, Hyderabad 500007, India.

出版信息

J Photochem Photobiol B. 2014 Dec;141:47-58. doi: 10.1016/j.jphotobiol.2014.09.003. Epub 2014 Sep 16.

Abstract

Three new ruthenium(II) polypyridyl complexes Ru(phen)2BrIPC (1), Ru(bpy)2 BrIPC (2) and Ru(dmb)2BrIPC (3) where, BrIPC = (6-bromo-3-(1H-imidazo[4,5-f] [1,10]-phenanthroline, phen = 1,10-phenanthroline, bpy = 2,2' bipyridine, dmb = 4,4'-dimethyl 2,2' bipyridine, were synthesised and characterised. DNA-binding nature was investigated by spectroscopic titrations and mode of binding was assessed by viscosity measurements. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be in the order of 10(5). Experimental results showed that these complexes interact with CT-DNA by intercalative mode. Photocleavage and antimicrobial activities were complex concentration dependent, at high concentration, high activity and vice versa. MTT assay was performed on HeLa cell lines, IC50 values of complexes in the order of 3 > 2 > 1 > cisplatin. From comet assay, cellular uptake studies, we observed that complexes could enter into the cell membrane and accumulate inside the nucleus. Molecular docking studies support the DNA binding affinity with hydrogen bonding and van der Waals attractions between base pairs and phosphate backbone of DNA with metal complexes.

摘要

合成并表征了三种新型钌(II)多吡啶配合物Ru(phen)2BrIPC(1)、Ru(bpy)2 BrIPC(2)和Ru(dmb)2BrIPC(3),其中,BrIPC = (6-溴-3-(1H-咪唑并[4,5-f][1,10]菲咯啉),phen = 1,10-菲咯啉,bpy = 2,2'-联吡啶,dmb = 4,4'-二甲基-2,2'-联吡啶。通过光谱滴定研究了DNA结合性质,并通过粘度测量评估了结合模式。配合物1、2和3的DNA结合常数Kb被确定为10(5)量级。实验结果表明,这些配合物通过插入模式与CT-DNA相互作用。光裂解和抗菌活性与配合物浓度有关,高浓度时活性高,反之亦然。对HeLa细胞系进行了MTT测定,配合物的IC50值顺序为3 > 2 > 1 > 顺铂。通过彗星试验、细胞摄取研究,我们观察到配合物可以进入细胞膜并在细胞核内积累。分子对接研究支持了DNA与金属配合物之间通过氢键以及碱基对与DNA磷酸骨架之间的范德华吸引力形成的结合亲和力。

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