摘要/Abstract

异噁唑啉是一类具有广泛生物活性的杂环化合物.采用活性亚结构拼接的思路，在前期研究基础上，设计合成了10个未见文献报道的新型3-[4-（1-哌嗪基）]苯基-5-（2-呋喃基）-4，5-二氢异噁唑啉衍生物3~12，其结构经IR、¹H NMR、¹³C NMR和HRMS确证.采用噻唑蓝（MTT）法测试了目标化合物的体外细胞毒活性（Hela、A549和SGC7901）.结果表明，该类化合物普遍具有良好的细胞毒活性，特别是化合物4、6和11对肿瘤细胞株的体外抑制活性与阳性对照药5-氟尿嘧啶相当.进一步的流式细胞分析结果表明，化合物4和11均能有效诱导肿瘤细胞株A549的死亡.
关键词: 二氢异噁唑啉, 合成, 细胞毒活性, 流式细胞分析
Dihydroisoxazoline is a heterocyclic compound with a variety of biological properties. In this study, ten new 3-(4-piperazinyl)phenyl-5-(2-furyl)-4,5-dihydroisoxazoline derivatives (3~12) have been prepared by the general principle of molecular hybridization based on former work. The structures were characterized by IR, ¹H NMR, ¹³C NMR and HRMS. In vitro cytotoxic activity against a panel of human tumor cell lines (Hela, A549 and SGC7901) was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The result indicated that dihydroisoxazoline derivatives showed potential cytotoxic activity, and the substituents of the NH group of piperazine ring had an obvious influence on cytotoxic activities. Especially, compound 4, 6 and 11 were found to be better inhibition against human tumor cell lines, which were found to be similar cytotoxic activity to positive control 5-fluorouracil. Further FACs analysis showed that compounds 4 and 11 significantly induced death in A549 cell.
Key words: dihydroisoxazoline, synthesis, cytotoxic activity, FACs analysis


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