摘要/Abstract

基于4-取代喹啉是一类重要的喹啉衍生物，采用活性亚结构拼接方法设计合成了24个4-硫醚取代喹啉化合物，通过多种谱学方法确证其结构，并初步评价了它们的抗真菌活性.结果表明，绝大多数目标化合物对每种供试真菌均表现出一定程度的抗菌活性，其中2-苯基-4-乙硫基喹啉（4a）、2-苯基-4-（异丙基硫基）-喹啉（4c）与2-苯基-4-（烯丙基硫基）-喹啉（4h）的活性相对较好的活性相对较好，对部分病原菌抑制作用等同或接近阳性药物嘧菌酯.初步构效分析表明：4-位不同硫醚取代能显著影响该类化合物的活性，一般脂肪族取代活性强于芳香族取代，空间位阻较小的取代基化合物活性强于位阻较大者，而芳香族取代中苯环的不同取代模式对活性的影响不大甚至是不利的.
关键词: 喹啉, 硫醚, 抗菌活性, 合成
Based on the scaffold of 4-substituted quinoline, twenty-four 4-thioquinoline compounds were designed and synthesized by molecular hybridization. Their structures were identified by ¹H NMR, ¹³C NMR and HRMS. Meanwhile, all target compounds were evaluated for antifungal activities. The results indicated that the majority of target compounds displayed some activity against each of the fungi. Among them, 4-(ethylthio)-2-phenylquinoline (4a), 4-(isopropylthio)-2-phenylquinoline (4c) and 4-(allylthio)-2-phenylquinoline (4h) were more potent than others, whose inhibition rates against some fungi were comparable to the positive drug azoxystrobin. The structure-activity relationship (SAR) showed that different substituents on 4-position could significantly affect activities. Generally, the presence of aliphatic group could be more beneficial to antifungal activity than aromatic group, and the activity weakened with an increase of steric hindrance. Moreover, the kinds and positions of substituents on the aromatic ring had little or negative effects on the activity.
Key words: quinoline, thioether, antifungal activity, synthesis


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