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采用分子模拟和多光谱方法研究阿米洛利的体外细胞毒性和 DNA/HSA 相互作用。

In vitro cytotoxicity and DNA/HSA interaction study of triamterene using molecular modelling and multi-spectroscopic methods.

机构信息

a Faculty of Chemistry , Bu-Ali Sina University , Hamedan , Iran.

b Research Center for Molecular Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.

出版信息

J Biomol Struct Dyn. 2019 Jun;37(9):2242-2253. doi: 10.1080/07391102.2018.1489305. Epub 2018 Nov 13.

Abstract

The anticancer activity of triamterene on HCT116 and CT26 colon cancer cells lines was investigated. Furthermore, the mechanism of interaction between triamterene and calf thymus DNA (ct-DNA) and also human serum albumin (HSA) was conducted using spectroscopic and molecular docking techniques. In vitro cytotoxicity of triamterene against HCT116 and CT26 cells showed promising anticancer effects with IC50 values of 31.30 and 24.45 μM, respectively. Competitive studies of the triamterene with NR (neutral red) and MB (methylene blue) as intercalator probes showed that triamterene can be replaced by these probes. The viscosity data also confirmed that triamterene binds to calf-thymus DNA through intercalation binding mode. Binding properties of triamterene with HSA in the presence of warfarin and ibuprofen showed that triamterene competes with warfarin for the site I of human serum albumin (HSA). In addition, the binding modes of triamterene with DNA and HSA were verified by molecular docking technique. Abbreviations ct-DNA calf thymus DNA CV cyclic voltammetry DNA deoxyribonucleic acid DPV differential pulse voltammetry FBS fetal bovine serum HSA human serum albumin NR neutral red MB methylene blue MTT 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide Communicated by Ramaswamy H. Sarma.

摘要

研究了阿米洛利对 HCT116 和 CT26 结肠癌细胞系的抗癌活性。此外,还使用光谱和分子对接技术研究了阿米洛利与小牛胸腺 DNA(ct-DNA)和人血清白蛋白(HSA)之间的相互作用机制。阿米洛利对 HCT116 和 CT26 细胞的体外细胞毒性显示出有希望的抗癌作用,IC50 值分别为 31.30 和 24.45 μM。阿米洛利与 NR(中性红)和 MB(亚甲蓝)作为嵌入探针的竞争性研究表明,阿米洛利可以被这些探针取代。粘度数据也证实,阿米洛利通过嵌入结合模式与小牛胸腺 DNA 结合。在华法林和布洛芬存在下,阿米洛利与 HSA 的结合特性表明,阿米洛利与华法林竞争人血清白蛋白(HSA)的位点 I。此外,还通过分子对接技术验证了阿米洛利与 DNA 和 HSA 的结合模式。缩写 ct-DNA 小牛胸腺 DNA CV 循环伏安法 DNA 脱氧核糖核酸 DPV 差分脉冲伏安法 FBS 胎牛血清 HSA 人血清白蛋白 NR 中性红 MB 亚甲蓝 MTT 3-(4,5-二甲基噻唑-2 基)-2,5-二苯基四唑溴盐由 Ramaswamy H. Sarma 传达。

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