Stagliano Kenneth W, Emadi Ashkan, Lu Zhenhai, Malinakova Helena C, Twenter Barry, Yu Min, Holland Louis E, Rom Amanda M, Harwood John S, Amin Ronak, Johnson Allison A, Pommier Yves
Department of Biological, Chemical and Physical Sciences, Illinois Institute of Technology, Chicago, 60616, USA.
Bioorg Med Chem. 2006 Aug 15;14(16):5651-65. doi: 10.1016/j.bmc.2006.04.034. Epub 2006 Jun 5.
Unsymmetrical biquinone and trimeric quinone derivatives were synthesized using halotriflate-biselectrophilic naphthoquinones through stepwise regioselective quinone substitution chemistry and evaluated for their ability to inhibit the cytopathogenic effects of HIV-1 using an MTT colorimetric assay. Compounds were also screened for their ability to inhibit the activity of HIV-1 integrase in vitro. Pyranylated trimeric quinones and biquinones exhibited both antiviral activity and integrase inhibitory activity. Conocurvone 1 and trimeric quinone 21 were the most potent HIV integrase inhibitors in the series. All of the biquinones showed HIV inhibitory activity. Simple methoxy substituted biquinones did not inhibit HIV-1 integrase.
通过逐步区域选择性醌取代化学，利用卤代三氟甲磺酸酯双亲电萘醌合成了不对称双醌和三聚醌衍生物，并使用MTT比色法评估了它们抑制HIV-1细胞病变效应的能力。还筛选了化合物在体外抑制HIV-1整合酶活性的能力。吡喃化三聚醌和双醌表现出抗病毒活性和整合酶抑制活性。Conocurvone 1和三聚醌21是该系列中最有效的HIV整合酶抑制剂。所有双醌均显示出HIV抑制活性。简单的甲氧基取代双醌不抑制HIV-1整合酶。
