Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives

doi:10.6023/cjoc201807022

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (3): 821-829.DOI: 10.6023/cjoc201807022 Previous Articles Next Articles

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新型异长叶烷基二氢嘧啶硫酮类衍生物的合成及其抗肿瘤活性研究

马崇慧^a, 吴陈亮^a, 王芸芸^a, 黄真真^b, 张强健^a, 董阜豪^a, 谷文^a,c, 单宇^b, 王石发^a,c

a 南京林业大学化学工程学院南京 210037;
b 江苏省中国科学院植物研究所南京 210014;
c 南京林业大学林业资源高效加工利用协同创新中心南京 210037

收稿日期:2018-07-11 修回日期:2018-09-24 发布日期:2018-10-20
通讯作者: 单宇, 王石发 E-mail:attilayu@hotmail.com;wangshifa65@163.com
基金资助:
国家自然科学基金（No.31470592）资助项目.

Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives

Ma Chonghui^a, Wu Chenliang^a, Wang Yunyun^a, Huang Zhenzhen^b, Zhang Qiangjian^a, Dong Fuhao^a, Gu Wen^a,c, Shan Y^b, Wang Shifa^a,c

a College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037;
b Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014;
c Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037

Received:2018-07-11 Revised:2018-09-24 Published:2018-10-20
Contact: 10.6023/cjoc201807022 E-mail:attilayu@hotmail.com;wangshifa65@163.com
Supported by:
Project supported by the National Natural Science Foundation of China (No. 31470592).

1. Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives.PDF(3870KB)

Abstract

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

Cite this article

Ma Chonghui, Wu Chenliang, Wang Yunyun, Huang Zhenzhen, Zhang Qiangjian, Dong Fuhao, Gu Wen, Shan Y, Wang Shifa. Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives[J]. Chin. J. Org. Chem., 2019, 39(3): 821-829.

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新型异长叶烷基二氢嘧啶硫酮类衍生物的合成及其抗肿瘤活性研究

Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives

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