Glycyrrhetinic acid: a promising scaffold for the discovery of anticancer agents

Abstract

Introduction: Oleanane-type pentacyclic triterpenes named glycyrrhetinic acids (GAs) featuring a C-30 carboxylic acid group, are extracted from the licorice (Glycyrrhiza uralensis). Numerous biological properties of GA have been reported and have attracted researchers from all over the world in recent years due to the peculiar GA scaffold-based semisynthetic cytotoxic effects.

Areas covered: This review represents the applications of semisynthetic derivatives of GA for the development of future cancer treatments. Included in the review are important structural features of the semisynthetic GAs crucial for cytotoxic effects.

Expert opinion: Numerous semisynthetic GA derivatives illustrated excellent cytotoxic effects toward various cancer cells. Notably the C-₃(OH) at ring A along with C_30-CO₂H at ring E as vital structural features, make GA very appealing as a lead scaffold for medicinal chemistry, since these two groups permit the creation of further chemical diversity geared toward improved cytotoxic effects. Furthermore, numerous GA derivatives have been synthesized and indicate that compounds featuring cyanoenone moieties in ring A, or compounds having the amino group or nitrogen comprising heterocycles and hybrids thereof, illustrate more potent cytotoxicity. Furthermore, GA has a great capability to be conjugated with other anticancer molecules to synergistically enhance their combined cytotoxicity.

Keywords: Glycyrrhetinic acid; cytotoxicity; derivatives; lead compounds; licorice; mode of action.