新型紫罗兰酮基双查尔酮缩氨基硫脲的合成及抗肿瘤活性

doi:10.11944/j.issn.1000-0518.2017.08.170022

摘要/Abstract

摘要：

根据活性亚结构拼接原理,通过紫罗兰酮与(取代)苯甲醛反应合成了紫罗兰酮基双查尔酮,然后经与氨基硫脲缩合得到一系列未见报道的新型含紫罗兰酮、查尔酮及氨基硫脲3种优势结构单元的杂化体,它们的化学结构经傅里叶变换红外光谱(FT-IR)、核磁共振波谱(¹H NMR、¹³C NMR)、元素分析及质谱(MS)等测试技术所证实。采用溴化噻唑蓝四氮唑(MTT)法初步测定其体外抗肿瘤活性(乳腺癌细胞(MCF-7),肝癌细胞(HepG2),肺癌细胞(A549)),结果表明,对于不同类型的肿瘤细胞,化合物展现较好的增殖抑制活性。尤其是化合物3a与3b对MCF-7细胞展现较强的抗增殖活性,半数致死量(IC₅₀)值分别为10.83和7.62 μmol/L,化合物3e对A549细胞显示一定的增殖抑制活性效果(IC₅₀值为13.36 μmol/L),化合物3f对HepG2细胞表现了高效的抗增殖活性(IC₅₀值为8.55 μmol/L)。目标物的抗增殖活性与紫罗兰酮结构及查尔酮环上不同电子效应的取代基有关。

关键词: 缩氨基硫脲, 查尔酮, 紫罗兰酮, 抗肿瘤活性, 合成

Abstract:

In this work, a variety of new thiosemicarbazone derivatives were prepared by combining ionoe with chalcone and thiosemicarbazide according to the structure-activity combination principle. The ionone-based dichalcones were firstly synthesized through the condensation of ionone and substituted benzaldehydes, followed by thiosemicarbazide to obtain the target products. Their structures were confirmed by fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance spectroscopy(¹H NMR and ¹³C NMR), elemental analysis, and mass spectrometry(MS). The in vitro antitumor activities against MCF-7(human breast cancer), HepG2(human liver cancer) and A549(human lung cancer) cells were tested using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) method. The bioassay results demonstrate that compounds 3a and 3b display highly effective antiproliferative effects against MCF-7 cells with half maximal inhibitory concentration(IC₅₀) values of 10.83 and 7.62 μmol/L, respectively. Compound 3e exhibits preferable antiproliferative activities against A549 cells with an IC₅₀ value of 13.36 μmol/L, while compound 3f shows the best inhibitory effect against HepG2 cells with an IC₅₀ value of 8.55 μmol/L. Antitumor experiments show that the activities of these compounds are mainly affected by ionone and substituted groups in aromatic rings of chalcone.

Key words: thiosemicarbazone, chalcone, ionone, antitumor activity, synthesis

刘长辉,文瑞明,贺淼,易先文,叶晓琴,方磊. 新型紫罗兰酮基双查尔酮缩氨基硫脲的合成及抗肿瘤活性[J]. 应用化学, 2017, 34(8): 899-904.

LIU Changhui,WEN Ruiming,HE Miao,YI Xianwen,YE Xiaoqin,FANG Lei. Synthesis and Antitumor Activities of Novel Thiosemicarbazone Derivatives with Ionone-Based Bischalcone[J]. Chinese Journal of Applied Chemistry, 2017, 34(8): 899-904.

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