2. Academic Validation
  3. Synthesis and antitumor effects of novel 18β-glycyrrhetinic acid derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A

Synthesis and antitumor effects of novel 18β-glycyrrhetinic acid derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A

  • Bioorg Chem. 2020 Oct;103:104187. doi: 10.1016/j.bioorg.2020.104187.
Min Huang 1,  Ping Gong 2,  Yuetong Wang 2,  Xiaorui Xie 2,  Zhuangshi Ma 1,  Qihao Xu 1,  Dan Liu 1,  Yongkui Jing 3,  Linxiang Zhao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 3 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: [email protected].
  • 4 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: [email protected].
PMID: 32890994 DOI: 10.1016/j.bioorg.2020.104187
Abstract

A series of novel 18β-glycyrrhetinic acid (GA) derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A were synthesized and evaluated for their antitumor activities. Compounds 5c and 5l showed stronger cytotoxicity than other compounds and reported GA analogue CDODA-Me (methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate). 5c and 5l induced Apoptosis in Cancer cells accompanying with c-Flip reduction and Noxa induction, associated with decreased HDAC3 expression and increased acetylation of H3. 5l displayed better stability properties than 5c and CDODA-Me in microsomes and plasma, 5l also showed favorable pharmacokinetic profiles and inhibited tumor growth in mice. Compound 5l represents a new type of GA derivatives with improved antitumor activity.

Keywords

18β-glycyrrhetinic acid; Anticancer; Apoptosis.

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