Department of Pharmaceutics, I.T., Banaras Hindu University , Varanasi, Uttar Pradesh , India.
J Enzyme Inhib Med Chem. 2013 Dec;28(6):1192-8. doi: 10.3109/14756366.2012.721783. Epub 2012 Sep 14.
In an attempt to develop potent anticancer agents, a series of 4-arylideneamino/cycloalkylidineamino-1, 2-naphthoquinone thiosemicarbazones were synthesized and characterized using FT-IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis. The compounds were screened for antiproliferative activity against three human cancer cell lines (Hep-G2, MG-63 and MCF-7) using the MTT assay. Significant anticancer activity was observed for several members of the series. The compounds 4-(3, 4, 5-trimethoxybenzylidene amino) 1, 2-naphthoquinone-2-thiosemicarbazone (TS10) and 4-(4-hydroxy-3-methoxy benzylideneamino) 1, 2-naphthoquinone-2-thiosemicarbazone (TS13) were active cytotoxic agents in all three cancer cell lines, with IC50 values in the range of 3.5-6.4 µM. Further evaluation of some of these potent cytotoxic compounds demonstrated their good safety profile in a normal cell line (MCF-12A). Docking experiments showed a good correlation between the predicted glide scores and the IC50 values of these compounds. In silico ADME studies revealed that these compounds can be used for second generation development.
为了开发有效的抗癌药物，我们合成并通过傅里叶变换红外光谱（FT-IR）、（1）H 核磁共振谱（1H NMR）、（13）C 核磁共振谱（13C NMR）和元素分析对一系列 4-芳亚氨基/环亚氨基-1,2-萘醌缩氨硫脲进行了结构表征。我们使用 MTT 法对这些化合物的三种人类癌细胞系（Hep-G2、MG-63 和 MCF-7）的增殖抑制活性进行了筛选。该系列的几种化合物表现出显著的抗癌活性。化合物 4-(3,4,5-三甲氧基苯亚甲基氨基)-1,2-萘醌-2-缩氨硫脲（TS10）和 4-(4-羟基-3-甲氧基苯亚甲基氨基)-1,2-萘醌-2-缩氨硫脲（TS13）对所有三种癌细胞系均具有有效的细胞毒性作用，IC50 值在 3.5-6.4 μM 范围内。对一些具有强大细胞毒性的化合物进行的进一步评估表明，它们在正常细胞系（MCF-12A）中具有良好的安全性特征。对接实验表明，这些化合物的预测 Glide 评分与 IC50 值之间存在良好的相关性。基于计算机的 ADME 研究表明，这些化合物可用于第二代开发。
