Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit

doi:10.6023/cjoc201811040

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (5): 1460-1468.DOI: 10.6023/cjoc201811040 Previous Articles Next Articles

Notes

含尿嘧啶结构单元二肽衍生物的设计、合成及生物活性研究

唐雪梅^a,b, 范莉^a, 张泽朝^a, 杨大成^a

a 西南大学化学化工学院重庆 400715;
b 西南大学生命科学学院重庆 400715

收稿日期:2018-11-30 修回日期:2019-01-26 发布日期:2019-02-19
通讯作者: 杨大成 E-mail:hxydc@swu.edu.cn
基金资助:
国家自然科学基金（No.21542003）和重庆市自然科学基金（No.cstc2016jcyjA0421）资助项目.

Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit

Tang Xuemei^a,b, Fan Li^a, Zhang Zechao^a, Yang Dacheng^a

a School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715;
b School of Life Sciences, Southwest University, Chongqing 400715

Received:2018-11-30 Revised:2019-01-26 Published:2019-02-19
Contact: 10.6023/cjoc201811040 E-mail:hxydc@swu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21542003) and the Natural Science Foundation of Chongqing City (No. cstc2016jcyjA0421).

1. Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit.PDF(2269KB)

Abstract

In order to explore a new type of anti-diabetic molecules, dipeptide derivatives containing uracil structural units were designed. The key intermediate S-thymine-L-cysteine (IM-2) was obtained from uracil, paraformaldehyde and cysteine through two step reactions, and then 16 dipeptide derivatives were successfully synthesized through amino protection, carboxylation and amino acid coupling. All new compounds have been characterized by ¹H NMR, ¹³C NMR and HRMS, and the peroxisome proliferator response element (PPRE) activated activity, α-glucosidase-rat inhibitory activity and dipeptidyl peptidase-4 (DPP-4) inhibitory activity were screened for all target molecules. The results showed that these molecules had weak above-mentioned activities, meanwhile the change trend of α-glucosidase-rat inhibitory activity of these molecules is opposite to that of PPRE agonistic activity and DPP-4 inhibitory activity. It maybe provides an idea for the research of designing novel polypeptide multi-target drugs.

Key words: diabetes, uracil, dipeptide derivative, peroxisome proliferator response element (PPRE), α-glucosidase-rat inhibitory activity, dipeptidyl peptidase-4 inhibitory activity

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Tang Xuemei, Fan Li, Zhang Zechao, Yang Dacheng. Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit[J]. Chin. J. Org. Chem., 2019, 39(5): 1460-1468.

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含尿嘧啶结构单元二肽衍生物的设计、合成及生物活性研究

Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit

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