Synthesis and Bioactivity of 8-Deaza Folic Acid Analogues of Thiophene

doi:10.6023/cjoc1203122

Chin. J. Org. Chem. ›› 2012, Vol. 32 ›› Issue (10): 1944-1950.DOI: 10.6023/cjoc1203122 Previous Articles Next Articles

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具噻吩环8-去氮杂叶酸类似物的合成及生物活性研究

周受辛^a, 田超^a, 郭莹^a, 王孝伟^a, 刘俊义^a,b, 张志丽^a

a 北京大学药学院化学生物学系北京 100191;
b 北京大学药学院天然药物与仿生药物国家重点实验室北京 100191

收稿日期:2012-03-12 修回日期:2012-05-11 发布日期:2012-06-04
通讯作者: 张志丽 E-mail:lilybmu@bjmu.edu.cn
基金资助:
国家自然科学基金(Nos. 21042009, 21172014)和国家科技部(No. 2009ZX09301-010)资助项目.

Synthesis and Bioactivity of 8-Deaza Folic Acid Analogues of Thiophene

Zhou Shouxin^a, Tian Chao^a, Guo Ying^a, Wang Xiaowei^a, Liu Junyi^a,b, Zhang Zhili ^a

a Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191;
b State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191

Received:2012-03-12 Revised:2012-05-11 Published:2012-06-04
Supported by:
Project supported by the National Science Foundation of China (Nos. 21042009, 21172014) and the Ministry of Science and Technology of China (No. 2009ZX09301-010).

Based on the action mechanism of methionine synthase and structures of inhibitors against dihydrofolic reductase, thiophene derivatives of 8-deaza folic acid were designed as dual-target inhibitors. Two target compounds were obtained by nitration, reduction, condensation, and hydrolysis with 2-thiophenecarboxylic acid as starting material, and were characterized by ¹H NMR, ¹³C NMR and MS techniques. The inhibitory activities against methionine synthase and recombinant human dihydrofolate reductase were determined. The target compounds showed inhibitory activity on both two enzymes. The IC₅₀s of one compound were 25.2 and 2.3 μmol/L against methionine synthase and recombinant human dihydrofolate reductase, respectively.

Key words: thiophene derivatives of 8-deaza folic acid, methionine synthase, dihydrofolate reductase, nitration, bioactivity

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Zhou Shouxin, Tian Chao, Guo Ying, Wang Xiaowei, Liu Junyi, Zhang Zhili . Synthesis and Bioactivity of 8-Deaza Folic Acid Analogues of Thiophene[J]. Chin. J. Org. Chem., 2012, 32(10): 1944-1950.

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具噻吩环8-去氮杂叶酸类似物的合成及生物活性研究

Synthesis and Bioactivity of 8-Deaza Folic Acid Analogues of Thiophene

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