Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives

• Published in: Bioorganic & medicinal chemistry letters 2015-02, Vol.25 (3), p.728-732
• Main Authors: Zhang, Hengyuan, Zhu, Peiqing, Liu, Jie, Lin, Yan, Yao, Hequan, Jiang, Jieyun, Ye, Wencai, Wu, Xiaoming, Xu, Jinyi
• Format: Article
• Language: English
• Subjects: 23-Hydroxybetulinic acid; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Antiproliferative activity; Antitumor activity; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Disease Models, Animal; Drug Screening Assays, Antitumor; Humans; In vivo; Liver Neoplasms - drug therapy; Melanoma, Experimental - drug therapy; Mice; Pyrazole; Pyrazoles - chemistry; Structure-Activity Relationship; Transplantation, Heterologous; Triterpenes - chemistry; Triterpenes - therapeutic use; Triterpenes - toxicity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.11.058

A collection of novel pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. The results showed compound 15e as an effective chemotherapeutic agent candidate. [Display omitted] A collection of pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited significant antiproliferative activity. Especially compound 15e displayed the most potent activity with the IC50 values of 5.58 and 6.13μM against B16 and SF763 cancer cell lines, respectively. Furthermore, the significant in vivo antitumor activity of 15e 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.