新型1,3,4-噻二唑衍生物的合成及抗肿瘤活性
Synthesis and Antiproliferative Activity of Novel 1,3,4-Thiadiazole Derivatives
Received date: 2015-07-29
Revised date: 2015-09-13
Online published: 2015-10-23
以取代的苯乙酸为起始原料, 通过成环、偶联、脱保护基并引入苯磺酰胺等反应得到了系列2,5-二取代-1,3,4-噻二唑类化合物, 并利用1H NMR, 13C NMR和HRMS对目标化合物进行了结构表征. 用四甲基偶氮唑盐(MTT)法测试了目标化合物体外抑制前列腺癌细胞(PC-3)、乳腺癌细胞株(MDA-MB-231)和白血病细胞(K562)等肿瘤细胞的增殖活性. 结果显示, 部分目标化合物具有较好的抗肿瘤细胞增殖活性, 其中(S)-N-(5-([1,1'-联苯]-4-基甲基)-1,3,4-噻二唑-2-基)-2-氨基-3-(4-溴苯基)丙酰胺(6a)和(S)-N-(5-([1,1'-联苯]-4-基甲基)-1,3,4-噻二唑-2-基)-2-氨基-3-苯基丙酰胺(6b)对K562细胞的活性与阳性对照药棉酚相当.
刘婷婷 , 万义超 , 方浩 . 新型1,3,4-噻二唑衍生物的合成及抗肿瘤活性[J]. 有机化学, 2016 , 36(2) : 417 -424 . DOI: 10.6023/cjoc201507038
Twenty eight novel 1,3,4-thiadiazole derivatives were synthesized using different phenylacetic acids as the starting material, followed by the reaction of cyclization, coupling, deprotection, and finally introduced different substituted benzenesulfonamides. The structures of all target compounds were identified by 1H NMR, 13C NMR and HRMS. The biological evaluation was performed on PC-3 (prostatic cancer cell), MDA-MB-231 (breast cancer cell) and K562 (chronic myelogenous leukemia cell) by 3-(4,5-dimethylthigal-2-yl)-2,5-(diphenyltetragalium) bromide (MTT) assay. The results suggested that some compounds exhibited good anti-proliferative activities against tumor cell lines. Especially, compounds 6a and 6b showed similar inhibitory activities against K562 cell compared with gossypol.
Key words： thiadiazole; anticancer activity; synthesis
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