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Synthesis and Biological Evaluation of Oxygen‐containing Heterocyclic Ring‐fused 23‐Hydroxybetulinic Acid Derivatives as Antitumor Agents
Author(s) -
Zhang Hengyuan,
Li Fangzheng,
Zhu Peiqing,
Liu Jie,
Yao Hequan,
Jiang Jieyun,
Ye Wencai,
Wu Xiaoming,
Xu Jinyi
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12543
Subject(s) - isoxazole , chemistry , in vivo , oxadiazole , biological activity , cancer cell lines , structure–activity relationship , cell culture , cancer , stereochemistry , liver cancer , in vitro , cancer cell , combinatorial chemistry , biochemistry , biology , organic chemistry , genetics , microbiology and biotechnology
A collection of isoxazole and oxadiazole substituted 23‐hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23‐hydroxybetulinic acid, especially 13e and 14a were about four‐ to sevenfold more potent against all tested cancer cell lines than 23‐hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure–activity relationships of these 23‐hydroxybetulinic acid derivatives were also discussed based on the present investigation.