Wenmin Tang

Shanghai Institute of Technology

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Zhenyuan Miao

Second Military Medical University

Yuelin Wu

Shanghai Institute of Technology

Chuanhao Wang

Max-Planck-Institut für Kohlenforschung

Keli Yang

Shanghai Institute of Technology

Shuang Ye

Shanghai Jiao Tong University

Rongxue Lv

Shanghai Institute of Technology

Jianjiang Ma

Shanghai Institute of Technology

Yanming Zhang

Chinese Academy of Sciences

Chuan Luo

China Resources (China)

Ying Wang

Huazhong Agricultural University

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Second Military Medical University

Shanghai Institute of Technology

East China University of Science and Technology

Chinese Academy of Sciences

Xuzhou Medical College

Second People’s Hospital of Huai’an

Zero to Three

Shanghai Jiao Tong University

Dalian Medical University

Ministry of Agriculture and Rural Affairs

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Discovery of Novel 3,11‐Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity

Chemistry & Biodiversity (2023)

Wenmin Tang Yanming Zhang Keli Yang Jianjiang Ma Lian Dong

Abstract Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11‐bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3‐monopeptide ester derivative. The in vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10 mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration‐dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11‐bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.

hERG

Cardiotoxicity

10.1002/cbdv.202200911

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Application of a fluorine strategy in the lead optimization of betulinic acid to the discovery of potent CD73 inhibitors

Steroids (2022)

Yanming Zhang Keli Yang Shuang Ye Wenmin Tang Xuliang Chang

Betulinic acid

5'-nucleotidase

IC50

Lead compound

10.1016/j.steroids.2022.109112

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Citations (4)