Molecules 2013, 18(7), 7761-7847; doi:10.3390/molecules18077761

In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids

1 Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217, USA 2 Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA
* Author to whom correspondence should be addressed.
Received: 20 May 2013; in revised form: 23 June 2013 / Accepted: 26 June 2013 / Published: 3 July 2013
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
PDF Full-text Download PDF Full-Text [1179 KB, uploaded 3 July 2013 11:06 CEST]
Abstract: Neglected Tropical Diseases (NTDs), like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs.
Keywords: antileishmanial activity; terpenoids; drug targets; docking; Leishmania

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Ogungbe, I.V.; Setzer, W.N. In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids. Molecules 2013, 18, 7761-7847.

AMA Style

Ogungbe IV, Setzer WN. In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids. Molecules. 2013; 18(7):7761-7847.

Chicago/Turabian Style

Ogungbe, Ifedayo V.; Setzer, William N. 2013. "In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids." Molecules 18, no. 7: 7761-7847.

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert