作者:Soraya Alnabulsi、Buthaina Hussein、Elham Santina、Izzeddin Alsalahat、Manikandan Kadirvel、Rachael N. Magwaza、Richard A. Bryce、Carl H. Schwalbe、Alex G. Baldwin、Ilaria Russo、Ian J. Stratford、Sally Freeman
DOI:10.1016/j.bmcl.2018.03.025
日期:2018.5
non-symmetrical furan amidines are potent inhibitors of NQO2 and here novel analogues are evaluated. The furan ring has been changed to other heterocycles (imidazole, N-methylimidazole, oxazole, thiophene) and the amidine group has been replaced with imidate, reversed amidine, N-arylamide and amidoxime to probe NQO2 activity, improve solubility and decrease basicity of the lead furan amidine. All compounds
NQO2酶(NRH:醌氧化还原酶2)的抑制剂在癌症化学疗法和疟疾中具有潜在用途。我们以前曾报道过,不对称的呋喃are是NQO2的有效抑制剂,此处对新型类似物进行了评估。呋喃环已更改为其他杂环(咪唑,N-甲基咪唑,恶唑,噻吩),am基已被亚氨酸酯,反向,、N-芳酰胺和a肟取代,以探测NQO2活性,提高溶解度并降低碱的碱性。呋喃am铅。所有化合物在光谱上都得到了充分表征,其出乎意料的产物N的结构通过X射线晶体学建立-羟基-4-(5-甲基-4-苯基呋喃-2-基)苯甲m。评价了类似物对NQO2的抑制,NQO2的活性低于呋喃铅lead。通过初步的分子对接和结合模式分析,合理化了呋喃-系列与NQO2的构效关系。此外,恶唑-类似物以0.3μM的IC 50值抑制恶性疟原虫的生长。