Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives
Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives
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新型β-咔啉1,3,4-恶二唑衍生物的设计、合成及生物活性评价
DOI：
10.3390/molecules22111811
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发表时间：
2017-11-01
期刊：
影响因子：
4.6
通讯作者：
Zhong, Guo-Hua
中科院分区：
文献类型：
--
作者：
Zhang, Zhi-Jun;Zhang, Jing-Jing;Zhong, Guo-Hua
设计并合成了一系列新的-卡波林1,3,4-恶二唑衍生物，并对其体外对Sf9细胞的细胞毒活性和对斜纹夜蛾的生长抑制活性进行了评价。生物测定结果表明，这些化合物大多具有良好的体外细胞毒活性。其中，化合物37的体外药效最高（IC50 = 3.93 M），是喜树碱（CPT）的5倍（IC50 = 18.95 M）。化合物5和37可诱导Sf9细胞凋亡和细胞周期阻滞，并可刺激Sf-caspase-1的活化。体内生物试验还表明，化合物5和37能显著抑制斜纹夜蛾幼虫的生长，降低幼虫和蛹的重量。基于这些生物测定结果，化合物5和37成为开发潜在昆虫生长抑制的先导化合物。
A series of novel -carboline 1,3,4-oxadiazole derivatives were designed and synthesized, and the in vitro cytotoxic activity against Sf9 cells and growth inhibitory activity against Spodoptera litura were evaluated. Bioassay results showed that most of these compounds exhibited excellent in vitro cytotoxic activity. Especially, compound 37 displayed the best efficacy in vitro (IC50 = 3.93 M), and was five-fold more potent than camptothecin (CPT) (IC50 = 18.95 M). Moreover, compounds 5 and 37 could induce cell apoptosis and cell cycle arrest and stimulate Sf-caspase-1 activation in Sf9 cells. In vivo bioassay also demonstrated that compounds 5 and 37 could significantly inhibit larvae growth of S. litura with decreasing the weight of larvae and pupae. Based on these bioassay results, compounds 5 and 37 emerged as lead compounds for the development of potential insect growth inhibitions.