CAJ | 학술논문

目的设计合成双二酮酸类化合物，并探讨此类化合物抑制 HIV-1整合酶活性的构效关系。 　　方法以甲基取代苯乙酮为起始原料，经溴代后与羟基取代苯乙酮反应生成乙酰基苄氧苯乙酮，然后在氢化钠作用下，脱去α氢后进攻草酸二乙酯生成双二酮酸酯，水解脱去酯基生成双二酮酸；经1H-NMR、IR和 MS验证化合物结构。ELISA法测定目标化合物对 HIV-1整合酶的抑制活性；采用高通量荧光法测定目标化合物对 HIV-1整合酶3'加工过程的抑制活性；测定目标化合物对 HIV假病毒的细胞活性。 　　结果合成了6个全新结构的二酮酸类化合物；体外整合酶活性评价结果表明，6个目标化合物对 HIV-1整合酶的活性 IC50≤20μg/ml，双二酮酸之间距离稍短的5a、5c、5d对3'加工过程有一定的活性，IC50约为40μg/ml。 　　结论6个新化合物对 HIV-1的活性主要表现在链转移过程。
목적설계합성쌍이동산류화합물，병탐토차류화합물억제 HIV-1정합매활성적구효관계。 　　방법이갑기취대분을동위기시원료，경추대후여간기취대분을동반응생성을선기변양분을동，연후재경화납작용하，탈거α경후진공초산이을지생성쌍이동산지，수해탈거지기생성쌍이동산；경1H-NMR、IR화 MS험증화합물결구。ELISA법측정목표화합물대 HIV-1정합매적억제활성；채용고통량형광법측정목표화합물대 HIV-1정합매3'가공과정적억제활성；측정목표화합물대 HIV가병독적세포활성。 　　결과합성료6개전신결구적이동산류화합물；체외정합매활성평개결과표명，6개목표화합물대 HIV-1정합매적활성 IC50≤20μg/ml，쌍이동산지간거리초단적5a、5c、5d대3'가공과정유일정적활성，IC50약위40μg/ml。 　　결론6개신화합물대 HIV-1적활성주요표현재련전이과정。
Objective To explore the relationship of structure and activity of these compounds with anti HIV-1 integrase through designing and synthesizing a series of novel bis-diketo acid compounds. Methods Title compounds were synthesized through bromination, substitution and hydrolyzation. 6 target compounds were obtained. All structures were confirmed by1H-NMR, IR and MS. Anti HIV-1 integrase activitiesin vitro of the target compounds were tested by ELISA, high-throughput fluorescence method was used to anti HIV-1 integrase 3P activities, and HIV-1 pseudovirus was applied to determine the infection rate of cells inhibited by the compounds. Results 6 novel compounds were synthesized. The title compounds exhibited moderate anti-integrase activity with IC50≤ 20μg/ml. Three target compounds exhibited 3P activity with IC50≈ 40μg/ml. Conclusion 6 novel compounds exihibit mainly ST activity. The study will help to understand the relationship of structure and activity of compounds with anti HIV-1 activities.