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Cytotoxic Cardenolides from Calotropis Species: A Short Review

Eric Wei Chiang Chan, Nuha I. Sweidan, Siu Kuin Wong and Hung Tuck Chan

Faculty of Applied Sciences, UCSI University, Cheras 56000, Kuala Lumpur, Malaysia

Department of Chemistry, University of Petra, Amman 961343, Jordan

School of Science, Monash University Sunway, Petaling Jaya 46150, Selangor, Malaysia

Secretariat, International Society for Mangrove Ecosystems, c/o Faculty of Agriculture, University of the Ryukyus, Okinawa 903-0129, Japan

Abstract: From different plant parts of Calotropis species (C. gigantea and C. procera), various classes of compounds such as oxy pregnanes, terpenoids, sterols, cardenolides and flavonoids have been isolated. Of these compounds, the cardenolides stand out as many of them have anticancer properties. Cardenolides are C 23 steroids with a five-membered unsaturated butyrolactone ring consisting of a steroid nucleus, a lactone moiety at C-17 and a sugar moiety at C-3. The roles of cardenolides in the treatment of human cancer have been established as they can induce apoptosis and inhibit the growth of cancer cells. Structure‒activity relationship analyses have yielded some interesting findings on their cytotoxicity. Compounds with six-membered ring sugar groups generally have significantly stronger inhibitory activity than those with five-membered ring sugar groups. A formyl or methyl-hydroxyl group at C-10 enhances cytotoxicity while the presence of a 4´-OH or 16-OH group decreases cytotoxicity. Chemical modification of 2”-oxovoruscharin, a novel cardenolide extracted from the root bark of C. procera, has led to the synthesis of UNBS1450. The compound is characterized by more potent anti-proliferative activity, lower toxicity, and is a strong sodium pump inhibitor and inducer of non-apoptotic cell death. UNBS1450 is currently in Phase I clinical trials.

Keywords: Calotropis gigantea; Calotropis procera; cytotoxicity; structure - activity relationship. © 2017 ACG Publications. All rights reserved.