Citation: Ma Chonghui, Wu Chenliang, Wang Yunyun, Huang Zhenzhen, Zhang Qiangjian, Dong Fuhao, Gu Wen, Shan Yu, Wang Shifa. Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives[J]. Chinese Journal of Organic Chemistry, ;2019, 39(3): 821-829. doi: 10.6023/cjoc201807022 shu

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 Yu ^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

Corresponding author: Shan Yu, attilayu@hotmail.com Wang Shifa, wangshifa65@163.com
Received Date: 11 July 2018
Revised Date: 24 September 2018
Available Online: 19 March 2018
Fund Project: the National Natural Science Foundation of China 31470592Project supported by the National Natural Science Foundation of China (No. 31470592)

Figures(4)

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.
- isolongifolanone,
- dihydropyrimidinethione derivatives,
- antitumor activity
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