Discovery of 1,3,4-Oxadiazole Derivatives Containing A Bisamide Moiety As a Novel Class of Potential Cardioprotective Agents

41 Pages Posted: 7 May 2022

See all articles by Fei Fei Yang

Fei Fei Yang

Zhengzhou University

Jin Zhu Zhou

Zhengzhou University

Xue Li Xu

Zhengzhou University

Ting Hu

Zhengzhou University

Jian Quan Liu

Zhengzhou University

Ya Xi Wu

Zhengzhou University

Bo Wei

Zhengzhou University

Liying Ma

Zhengzhou University

Abstract

Myocardial injury is a nonnegligible problem in cardiovascular diseases and cancer therapy. The functional feature of N-containing heterocycles in cardiovascular field has attracted much attention in recent years. Herein, we discovered a lead compound 12a containing 1,3,4-oxadiazole by extensive screening of anticancer derivatives containing nitrogen-heterocycle, which exhibited potential protective activity against oxidative stress in cardiomyocytes. Follow-up structure-activity relationship (SAR) studies also highlighted the role played by substitution sites and bisamide moiety in enhancing the protective activity against oxidative stress. Specifically, compound 12d exhibited low cytotoxicity under high concentration and potent myocardial protection against oxidative stress in H9c2 cells. Preliminary mechanistic studies showed compound 12d could decrease expression of cardiac hypertrophy and oxidative stress related proteins/genes and reduce mitochondria-mediated cell apoptosis, thereby enhancing the cell vitality of injured cardiomyocytes. In this study, 1,3,4-oxadiazole may represent a novel pharmacophore that possesses potential myocardial protection and provides more choices for future optimization of cardiovascular drugs, especially for the treatment of onco-cardiology.

Keywords: 1, 3, 4-oxadiazole, Myocardial injury, Cardioprotective agents, Onco-cardiology

Suggested Citation

Yang, Fei Fei and Zhou, Jin Zhu and Xu, Xue Li and Hu, Ting and Liu, Jian Quan and Wu, Ya Xi and Wei, Bo and Ma, Liying, Discovery of 1,3,4-Oxadiazole Derivatives Containing A Bisamide Moiety As a Novel Class of Potential Cardioprotective Agents. Available at SSRN: https://ssrn.com/abstract=4102753 or http://dx.doi.org/10.2139/ssrn.4102753

Fei Fei Yang

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Jin Zhu Zhou

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Xue Li Xu

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Ting Hu

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Jian Quan Liu

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Ya Xi Wu

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Bo Wei

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

Liying Ma (Contact Author)

Zhengzhou University ( email )

100 Science Avenue
Zhengzhou, CO 450001
China

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