Synthesis and Evaluation of Gambogic Acid Derivatives as Antitumor Agents. Part III

• Published in: Chemistry & biodiversity Vol. 10; no. 1; pp. 73 - 85
• Main Authors: Guo, Xiao-Ke, Sun, Hao-Peng, Shen, Shen, Sun, Yuan, Xie, Fan-Lei, Tao, Lei, Guo, Qing-Long, Jiang, Cheng, You, Qi-Dong
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01.01.2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Annexin A5 - metabolism; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Antitumor activity; Apoptosis; Apoptosis - drug effects; Apoptosis-inducing activity; Cell Line, Tumor; Gambogic acid; Hep G2 Cells; Humans; Proteins; Structure-Activity Relationship; Structureactivity relationship (SAR); Xanthones - chemical synthesis; Xanthones - chemistry; Xanthones - toxicity
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.201200126

Gambogic acid (GA) has been reported as a potent apoptosis inducer. Previously, we have reported chemical modification at C(34) and C(39) of GA, leading to some agents with improved activity. To investigate the further structureactivity relationship (SAR) and preliminary mechanism of GA activity, a series of derivatives with modified prenyl side chains of GA were synthesized and evaluated. Most of the derivatives showed potent inhibitory activities against the proliferation of HepG2 and A549 cell lines. Compound 4 was selected for further mechanistic studies due to its outstanding activity. It was established that 4 induces the apoptosis of HepG2 cells by using Annexin‐V/PI double staining and Western blot assay, thus, compound 4 can serve as a promising lead compound for the development of novel apoptosis in anticancer treatment.