Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017)

ABSTRACT

Introduction: Glycyrrhetinic acids (GAs) viz., 18β-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity.

Areas covered: This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs.

Expert opinion: GAs demonstrate excellent cytotoxic, antimicrobial, enzyme inhibitory, antiinflammatory, antioxidant, analgesic, and antiviral effects. It is interesting to note that the C-₃(OH) and C_30-CO₂H functional groups make GAs very attractive lead structures for medicinal scientists since these functionalities allow the generation of further chemical diversity for improved pharmacological effects. Moreover, various GA analogues have been prepared via modification of the C_30-CO₂H. It is noteworthy that the C-30 amide of GA demonstrated better cytotoxic effects compared to the parent compounds. In addition, GAs have the capability to conjugate with other anticancer drugs or be converted into their halo or amino analogs which is expected to stimulate medicinal chemist to synthesize new lead compounds in cancer drug discovery.

KEYWORDS:

• Glycyrrhetinic acids
• cytotoxic
• antimicrobial
• anti-inflammatory
• diabetes

Article highlights

• Glycyrrhetinic acids (GAs) are a class oleanane-type triterpenes that occur in nature and may be chemically transformed in order to create a broader chemical diversity.

• This review outlines the synthetic and biological investigations from 2010–2017 in the development of GAs for cytotoxic, antimicrobial, antiinflammatory, and other therapuetic potentials.

• Most applications of GAs are associated for the treatment of various cancers.

• Modifying GAs at positions C₃-OH, and C₃₀-CO₂H greatly improves their biological and pharmaceutical effects.

• Conjugates of GAs with other bioactive compounds are discussed.

• Gas demonstrate great potential in the treatment of cancer, inflammation, and diabetes.

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

Additional information

Funding

This paper has not been funded.