Cytotoxic cardenolides from Calotropis gigantea

• Published in: Phytochemistry (Oxford) 2021-12, Vol.192, p.112951-112951, Article 112951
• Main Authors: He, Yi-Lin, Yang, Hong-Ying, Huang, Pei-Zhi, Feng, Wei-Jiao, Gao, Kun
• Format: Article
• Language: English
• Subjects: Asclepiadaceae; Calotropis gigantea; Cardenolides; Cell cycle; Cytotoxicity
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2021.112951

Sixteen cardiac glycosides, including five previously undescribed compounds, were extracted and purified from whole plants of Calotropis gigantea (L.). Spectroscopic data and electronic circular dichroism (ECD) analyses were used to determine their structures. Calogiganin C is the first naturally occurring example of a cardenolide containing a 7-membered lactone in ring A. The cytotoxic activities of these compounds against A172, U251, AGS, PANC-1, HepG2, HCT116 and NCI-H226 cell lines were evaluated. Four of them exhibited the most potent growth inhibitory activity against a panel of human cancer cell lines, including A172, U251, AGS, PANC-1 and HCT116. Notably, uscharidin and calotropin showed pronounced cytotoxicities at low nanomolar concentrations against A172 and U251 cells, and possible cell death mechanism studies manifested that these two compounds induced G2/M cell cycle arrest, which demonstrated promising anticancer potential. Cardiac glycosides from the whole plant of Calotropis gigantea (L.), collected from Hainan Province, China. [Display omitted] •Five undescribed cardenolides were isolated from Calotropis gigantea (L.).•Calogiganin C is the first natural cardenolide containing 7-membered lactone in ring A.•Uscharidin and calotropin exhibited most potential cytotoxicities against A172 and U251 cells.•Treatment of A172 cells with uscharidin or calotropin leaded to the significant arrest of the cell cycle on G2/M.