Ursolic acid derivatives for pharmaceutical use: a patent review (2012-2016)

ABSTRACT

Introduction: Ursolic acid (UA), belongs to a group of pentacyclic triterpenoids and is known to possess some very interesting biological properties. Protocols have been developed in order to synthesize bioactive UA analogs which have resulted in numerous ursolic acid analogs being synthesized during the period 2012–2016. Ursolic acid and its analogues can be employed to treat various cancers, inflammatory diseases, diabetes, Parkinson’s disease, Alzheimer’s disease, hepatitis B, hepatitis C and AIDS to mention but a few.

Areas covered: This review covers patents on therapeutic activities of ursolic acid (UA) and its synthetic derivatives published during the four year period 2012–2016. A discussion about structure-activity relationships (SAR) of these analogs is also included.

Expert opinion: Ursolic acid and its synthetic derivatives demonstrated excellent anticancer, antidiabetic, antiarrhythmic, anti-hyperlipidemic, antimicrobial, anti-hypercholesterolemic, and anti-cardiovascular properties. Additionally, various ursolic acid analogues have been synthesized through modification at positions C₂-OH, C₃-OH and C_17-CO₂H. It is noteworthy that the C-17 amide and amino analogs of UA possessed better anticancer activity compared to the parent compound (UA). Most importantly, UA has the potential to conjugate with other anticancer drugs or be transformed into its halo derivatives since this will greatly facilitate scientists to get lead compounds in cancer drug discovery.

KEYWORDS:

• Ursolic acid
• anticancer
• anti-inflammatory
• diabetes
• in vitro
• in vivo

Article highlights

• Ursolic acid derivatives are a class of compound that occur in nature and can be modified chemically in order to generate a broader chemical diversity.

• This review describes the synthetic and biological efforts over a four year period (2012-2016) in the development of ursolic acid and its semi-synthetic analogs for anticancer, anti-inflammatory, and antidiabetic potency.

• Modifying ursolic acid via C₂-OH, C₃-OH, and C₁₇-CO₂H into other important pharmacophores results in the enhancement of their biological and pharmaceutical potency.

• Ursolic acid and its synthetic derivatives have 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 other 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 apart from those disclosed.

Dedication

Dedicated to Professor Atta-ur-Rahman on the occasion of his 75th birthday.

Additional information

Funding

This paper was not funded.