A Review on Structure-Activity Relationships of Glycyrrhetinic Acid Derivatives with Diverse Bioactivities

Abstract

Pentacyclic triterpenoids, consisting of six isoprene units, are a kind of natural active substance. At present, numerous pentacyclic triterpenes have been identified and classified into four subgroups of oleanane, ursane, lupane, and xylene on the basis of the carbon skeleton. Among them, oleanane is the most popular due to its rich backbone and diverse bioactivities. 18β-Glycyrrhetinic acid (GA), an oleanane-type pentacyclic triterpene isolated from licorice roots, possesses diverse bioactivities, including antitumor, anti-inflammatory, antiviral, antimicrobial, enzyme inhibitor, hepatoprotective, and so on. It has received more attention in medicinal chemistry due to the advantages of easy access and rich bioactivity. Thus, numerous novel lead compounds have been synthesized using GA as a scaffold. Herein, we summarize the structure-activity relationship and synthetic methodologies of GA derivatives from 2010 to 2020, as well as the most active GA derivatives. Finally, we anticipate that this review can benefit future research on structural modifications of GA to enhance bioactivity and provide an example for developing pentacyclic triterpene-based novel drugs.

Keywords: Glycyrrhetinic acid; bioactivities; natural products; structural modifications; structure-activity relationship; synthesis.