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Mini-Reviews in Medicinal Chemistry

Eiditor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

The Promise of Plant-Derived Substances as Inhibitors of Arginase

Author(s): C. Girard-Thernier, T.-N. Pham and C. Demougeot

Volume 15 , Issue 10 , 2015

Page: [798 - 808] Pages: 11

DOI: 10.2174/1389557515666150511153852

Price: $58

Abstract

The enzyme arginase catalyses the divalent cation dependent hydrolysis of L-arginine to produce L-ornithine and urea. Two isoforms of arginases have been identified in mammalian (including human) cells. Moreover, some infectious pathogens (e.g. Leishmania) synthesize their own arginase. Work over the last decades has revealed that elevated arginase activity both decreases cellular availability in nitric oxide (NO) by competing with NO synthases (NOS) and increases concentration in L-ornithine, a precursor in the biosynthesis of polyamines which are important for cell differentiation and proliferation. From these data emerged the concept that selective arginase inhibitors might be a valuable strategy for treatment of various diseases associated with decreased NO and/or increased polyamines production. Consistent with this, recent research provides compelling evidence supporting the beneficial effects of arginase inhibitors in cardiovascular diseases (hypertension, ischemia reperfusion injury, atherosclerosis, diabetes mellitus), asthma, cancer, immunologically-mediated diseases or leishmaniasis. Despite active programs to identify potent arginase inhibitors, effective chemical compounds with reliable pharmacokinetics and toxicological properties are rare. The present review summarizes available data on the discovery of new arginase inhibitors from natural origin. Current knowledge on plant-derived compounds or extracts with arginase inhibitory properties as well as available data on structure-activity relationship (SAR) will be presented. Lastly, the present review will open up new prospects in order to improve the discovery of novel arginase inhibitors from natural sources.

Keywords: Arginase inhibitors, cardiovascular diseases, leishmaniasis, natural substances, polyphenols.


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