From different plant parts of Calotropis species (C. gigantea and C. procera), various classes of compounds such as oxypregnanes, terpenoids, sterols, cardenolides and flavonoids have been isolated. Of these compounds, the cardenolides stand out as many of them have anticancer properties. Cardenolides are C23 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 antiproliferative 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. [ABSTRACT FROM AUTHOR]