Cytotoxic Cardenolides from Calotropis Species: A Short Review

Abstract

Abstract: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 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 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.

Triple-Negative Breast Cancer Cells Exhibit Differential Sensitivity to Cardenolides from Calotropis gigantea

“…Calotropis gigantea , which is commonly known as the “giant milk weed” or “crown flower”, is found across South and Southeast Asia, as well as Africa, and is known for its many medicinal uses . Numerous metabolites that likely contribute to its reported medicinal properties have been isolated from Calotropis species, including sterols, flavonoids, oxypregnanes, terpenoids, and cardenolides, many of which have cytotoxic effects against cancer cells . Recently, six new cardenolides were isolated from C. gigantea , several of which displayed sub-micromolar potency against a pancreatic cancer cell line .…”

“…15 Numerous metabolites that likely contribute to its reported medicinal properties have been isolated from Calotropis species, including sterols, flavonoids, oxypregnanes, terpenoids, and cardenolides, many of which have cytotoxic effects against cancer cells. 16 Recently, six new cardenolides were isolated from C. gigantea, several of which displayed sub-micromolar potency against a pancreatic cancer cell line. 17 Given this background, we speculated that cardenolides might be responsible for the selective activity of the C. gigantea crude extract.…”

A review on phytochemical constituents and pharmacological potential ofCalotropis procera

“… 160 Cardenolides are C23 steroids with steroid nucleus having a glycoside moiety at C-3 and a lactone moiety at C-17. 6 Cardiac glycosides can be novel antineoplastic agents as cancer cells are more prone to these compounds. 159 Terpenoids (ursane, olenane type and pentacyclic triterpenes etc. )…”

“…These oxypregnanes have benzoyl moiety at C-12 and a straight 5–7 units sugar chain connected to C-3 of the aglycone. 6 Some glycosides ( Fig. 6 ), lignan glycosides ( Fig.…”

“…Earlier reviews 6–16 have discussed on phytochemistry, ethnobotany and pharmacological potential of Calotropis procera . Review on Calotropis species 17–20 comparing procera and gigantea have deliberated their therapeutic importance.…”