New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium

The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participa...

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Main Authors:	Saggu, Gagandeep S., Pala, Zarna R., Garg, Shilpi, Saxena, Vishal
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020098/

id	pubmed-5020098
recordtype	oai_dc
spelling	pubmed-50200982016-09-27 New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium Saggu, Gagandeep S. Pala, Zarna R. Garg, Shilpi Saxena, Vishal Microbiology The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures. Fosmidomycin is now-a-days prescribed clinically, however, less absorption, shorter half-life, and toxicity at higher doses, limits its use as an anti-malarial. The potential of other enzymes of the pathway as candidate drug targets has also been determined. This review details the various drug molecules tested against these targets with special emphasis to Plasmodium. We corroborate that MEP pathway functional within the apicoplast of Plasmodium is a major drug target, especially during erythrocytic stages. However, the major bottlenecks, bioavailability and toxicity of the new molecules needs to be addressed, before considering any new molecule as a potent antimalarial. Frontiers Media S.A. 2016-09-13 /pmc/articles/PMC5020098/ /pubmed/27679614 http://dx.doi.org/10.3389/fmicb.2016.01421 Text en Copyright © 2016 Saggu, Pala, Garg and Saxena. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Saggu, Gagandeep S. Pala, Zarna R. Garg, Shilpi Saxena, Vishal
spellingShingle	Saggu, Gagandeep S. Pala, Zarna R. Garg, Shilpi Saxena, Vishal New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium
author_facet	Saggu, Gagandeep S. Pala, Zarna R. Garg, Shilpi Saxena, Vishal
author_sort	Saggu, Gagandeep S.
title	New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium
title_short	New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium
title_full	New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium
title_fullStr	New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium
title_full_unstemmed	New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium
title_sort	new insight into isoprenoids biosynthesis process and future prospects for drug designing in plasmodium
description	The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures. Fosmidomycin is now-a-days prescribed clinically, however, less absorption, shorter half-life, and toxicity at higher doses, limits its use as an anti-malarial. The potential of other enzymes of the pathway as candidate drug targets has also been determined. This review details the various drug molecules tested against these targets with special emphasis to Plasmodium. We corroborate that MEP pathway functional within the apicoplast of Plasmodium is a major drug target, especially during erythrocytic stages. However, the major bottlenecks, bioavailability and toxicity of the new molecules needs to be addressed, before considering any new molecule as a potent antimalarial.
publisher	Frontiers Media S.A.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020098/
_version_	1613649566411784192

New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium

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