噻二唑类肽衍生物的合成及抗肿瘤增殖活性研究
收稿日期: 2016-06-11
修回日期: 2016-06-27
网络出版日期: 2016-08-25
基金资助
国家自然科学基金面上（No. 81373281）、山东省自然科学杰出青年基金（No. JQ201319）及国家级大学生创新创业训练计划（No. 10000072188007）资助项目.
Synthesis and Antiproliferative Activity of Thiadiazole Peptidomimetic Derivatives
Received date: 2016-06-11
Revised date: 2016-06-27
Online published: 2016-08-25
Supported by
Project supported by the National Natural Science Foundation China (No. 81373281), the Shandong Natural Science Foundation for Distinguished Young Scholars (No. JQ201319) and the National College Students Foundation for Innovation and Entrepreneurship Training Program (No.10000072188007).
以取代的苯乙酸、2-氨基硫脲为起始原料，经多步反应制备了一系列结构新颖的噻二唑类肽衍生物，其结构经1H NMR，13C NMR，HRMS确证.目标化合物应用3-（4，5-二甲基-2-噻唑基）-2，5-二苯基溴化四唑（MTT）法初步测试了抑制人白血病细胞（K562细胞）及前列腺癌细胞（PC-3细胞）增殖的活性，结果表明大部分目标化合物具有良好的抗肿瘤细胞增殖活性.针对5个活性目标化合物又进行了三株肿瘤细胞的深入活性评价，发现目标化合物（S）-（2-（（1-（（5-（1，1'-联苯-4-基甲基）-1，3，4-噻二唑-2-基）氨基）-1-氧亚基-3-苯基丙-2-基）氨基）-2-氧亚基乙基）氨基甲酸叔丁酯（6d）的活性最好，其抑制前列腺癌细胞（PC-3细胞）增殖的活性优于阳性药AT-101.
关键词： 噻二唑类肽衍生物; 抗肿瘤增殖活性; 前列腺癌细胞(PC-3细胞)
梁涛 , 李嘉杰 , 方金玉 , 刘婷婷 , 方浩 . 噻二唑类肽衍生物的合成及抗肿瘤增殖活性研究[J]. 有机化学, 2016 , 36(12) : 2895 -2905 . DOI: 10.6023/cjoc201606017
A series of thiadiazole peptidomimetic derivatives were prepared using different phenylacetic acids and thiosemicarbazide as the starting materials and followed by multi-step reactions. The structures of target compounds were identified by 1H NMR, 13C NMR and HRMS. The preliminary biological evaluations were performed on chronic myelogenous leukemia cell (K562 cell) and prostatic cancer cell (PC-3 cell) with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results suggested that most of target compounds have good antiproliferative activities against K562 cell. Further evaluations focused on the five active compounds using three tumor cell lines and found that (S)-tert-butyl(1-((2-((5-([1,1'-biphenyl]-4-ylmethyl)-1,3,4-thiadiazol-2-yl)amino)-2-oxoethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (6d) exhibited better antiproliferative activities against prostatic cancer cell (PC-3 cell) compared with AT-101.
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