Synthesis and antitumor activity of novel 3-oxo-23-hydroxybetulinic acid derivatives

Hengyuan Zhang; Peiqing Zhu; Jie Liu; Xue Yang; Shengtao Xu; Hequan Yao; Jieyun Jiang; Wencai Ye; Xiaoming Wu; Jinyi Xu

doi:10.1016/j.ejmech.2014.09.058

Synthesis and antitumor activity of novel 3-oxo-23-hydroxybetulinic acid derivatives

Eur J Med Chem. 2014 Nov 24:87:159-67. doi: 10.1016/j.ejmech.2014.09.058. Epub 2014 Sep 18.

Authors

Hengyuan Zhang¹, Peiqing Zhu¹, Jie Liu², Xue Yang¹, Shengtao Xu¹, Hequan Yao³, Jieyun Jiang⁴, Wencai Ye⁵, Xiaoming Wu¹, Jinyi Xu⁶

Affiliations

¹ State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
² State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Organic Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
³ State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address: [email protected].
⁴ Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
⁵ College of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, PR China.
⁶ State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address: [email protected].

PMID: 25247772
DOI: 10.1016/j.ejmech.2014.09.058

Abstract

A series of novel derivatives of 3-oxo-23-hydroxybetulinic acid was designed, synthesized, and evaluated for their antiproliferative activity against a panel of cancer cell lines (HL-60, BEL-7402, SF-763, HeLa, B16 and A375). The results indicated that majority of the derivatives exhibited more significant antitumor activity than the parent compound. In particular compound 10e showed the most potent activity with IC50 values of 5.85, 6.23 and 7.22 μM against B16, SF-763 and BEL-7402 cells, respectively. Furthermore, 10e inhibited tumor growth by 51.8% and 62.7% (w/w) in H22 and B16 xenograft mouse models, comparable to cyclophosphamide and 5-fluorouracil, respectively.

Keywords: 3-Oxo-23-hydroxybetulinic acid; Antiproliferative activity; Antitumor activity; B16 melanoma; Chemical modification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / pathology
Cell Proliferation / drug effects
Humans
Liver Neoplasms / drug therapy*
Liver Neoplasms / pathology
Melanoma, Experimental / drug therapy*
Melanoma, Experimental / pathology
Mice
Molecular Structure
Neoplasms / drug therapy*
Neoplasms / pathology
Structure-Activity Relationship
Triterpenes / chemistry*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

3-oxo-23-hydroxybetulinic acid
Antineoplastic Agents
Triterpenes