摘要/Abstract

以异长叶烷酮为起始物，经羟醛缩合、环化等手段，合成了12种异长叶烷基二氢嘧啶硫酮类衍生物，通过¹H NMR、¹³C NMR及高分辨质谱（HRMS）对其结构进行了表征，通过X射线衍射分析测定了化合物3e的晶体结构.探索了这些衍生物对人乳腺癌细胞（MDA-MB-231）、人宫颈癌细胞（HeLa）、人肝癌细胞（HepG-2）等三种癌细胞和一种正常细胞即小鼠巨噬细胞（RAW-264.7）的体外抗增殖活性.结果表明，这12种化合物显示出较好的抗肿瘤活性，其IC₅₀值在3.12~44.28 μmol/L范围内.其中，化合物3j对MDA-MB-231细胞表现出最强的抗肿瘤活性（IC₅₀=3.12 μmol/L），化合物3g对HeLa细胞表现出最强的抗肿瘤活性（IC₅₀=4.04 μmol/L），化合物3k对HepG-2细胞表现出最强的抗肿瘤活性（IC₅₀=5.43 μmol/L）.此外，化合物3j将MDA-MB-231细胞阻滞在G0/G1期，并以剂量依赖的方式诱导MDA-MB-231细胞的早期凋亡.
关键词: 异长叶烷酮, 二氢嘧啶硫酮类衍生物, 抗肿瘤活性
In this work, twelve dihydropyrimidinethione derivatives have been synthesized from isolongifolanone by aldol and cyclization reactions. The chemical structures were characterized by ¹H NMR, ¹³C NMR and high resolution mass spectrometry (HRMS), and the structure of compound 3e was determined by X-ray single crystal diffraction. Their in vitro cytotoxicity against three cancer cell lines breast (MDA-MB-231), cervix (HeLa), liver (HepG-2) and one normal cell line mouse macrophages (Raw-264.7) were investigated. It was shown that these 12 compounds had good antitumor activity with IC₅₀ values of 3.12~44.28 μmol/L. Among them, compounds 3j, 3g, and 3k had the best antitumor activity against MDA-MB-231 cells (IC₅₀=3.12 μmol/L), HeLa cells (IC₅₀=4.04 μmol/L) and HepG-2 cells (IC₅₀=5.43 μmol/L), respectively. In addition, compound 3j arrested the cells in the G0/G1 phase of the MDA-MB-231 cell cycle and induced the early apoptosis of MDA-MB-231 cells in a dose-dependent manner.
Key words: isolongifolanone, dihydropyrimidinethione derivatives, antitumor activity


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