Journal of Guangxi Normal University(Natural Science Edition) ›› 2021, Vol. 39 ›› Issue (2): 132-138.doi: 10.16088/j.issn.1001-6600.2020011603

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Synthesis and Antitumor Activity Evaluation of Oleanolic Acid-p-hydroxybenzonitrile and Its Analogues

LIU Jingjing1,2, CHEN Zhuanxin1,2, YOU Jiahang1,2, HUANG Jiayan1,2, CHENG Keguang1,2*   

  1. 1. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources Guangxi Normal University, Guilin Guangxi 541004, China;
    2. School of Chemistry and Pharmacy, Guangxi Normal University, Guilin Guangxi 541004, China
  • Received:2020-01-16 Revised:2020-03-03 Online:2021-03-25 Published:2021-04-15

Abstract: Oleanolic acid, ursolic acid and glycyrrhetinic acid were esterified with corresponding α,ω-dibromoalkane in the presence of potassium carbonate to prepare intermediates. Then, the intermediates were treated with p-hydroxybenzonitrile under potassium carbonate by means of a nucleophilic substitution reaction to generate six oleanolic acid/ursolic acid/glycyrrhetinic acid-p-hydroxybenzonitrile derivatives. Anti-tumor activity was tested by the MTT assay. The results showed that glycyrrhetinic acid-p-hydroxybenzonitrile conjugates [n-(4-cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate and [n-(4-cyanophenoxy)-octyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate had certain anti-proliferative effect on chronic myeloid leukemia cell line K562. Moreover, [n-(4-cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate also had moderate anti-proliferative effect on human liver tumor cell line Bel-7402. Other compounds had no antiproliferative activity on the tested cell lines. [n-(4-Cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate, which has less damage to normal liver cells, expressed almost the same level as the positive control drug 5-FU on the anti-proliferative activity of the tested cells. This indicated that [n-(4-cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oateand had the potential value for further research in anti-tumor field.

Key words: oleanolic acid, ursolic acid, glycyrrhetinic acid, p-hydroxybenzonitrile, antitumor activity

CLC Number: 

  • R914
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