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
• derivatives
• licorice
• cytotoxicity
• mode of action
• lead compounds

Article highlights

• Glycyrrhetinic acid (GA) has great potential as a scaffold to generate an intriguing chemical diversity of new structures.

• This review outlines the GA semisynthetic derivatives in the establishment of GAs for cytotoxic potential

• Modifying GA at the C₃-OH, and C₃₀-CO₂H functional groups greatly enhances their cytotoxic effects

• GA derivatives featuring cyanoenone, amino group, or nitrogen comprising heterocycles illustrated better cytotoxic effects

• Conjugates of GAs with various bioactive molecules is discussed

• GA derivatives illustrate great potential to treat various cancer

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.