Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies

Cofactor-independent phosphoglycerate mutase has been proposed as a therapeutic target for the treatment of trypanosomatid diseases. In this paper, we report the identification of compounds that could potentially be developed as selective inhibitors of cofactor-independent phosphoglycerate mutase fr...

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Main Authors:	Ahmad Fuad, Fazia Adyani, Houston, Douglas Robert, Michels, Paul A M, Fothergill- Gilmore, Linda A., Walkinshaw, Malcolm Douglas
Format:	Article
Language:	English English English
Published:	Penerbit Universiti Kebangsaan Malaysia 2016
Subjects:	TA Engineering (General). Civil engineering (General) TA164 Bioengineering
Online Access:	http://irep.iium.edu.my/53866/ http://irep.iium.edu.my/53866/ http://irep.iium.edu.my/53866/1/53866_Inhibitors%20of%20Leishmania.pdf http://irep.iium.edu.my/53866/2/53866_Inhibitors%20of%20Leishmania_WOS.pdf http://irep.iium.edu.my/53866/4/53866_Inhibitors%20of%20Leishmania_SCOPUS.pdf

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spelling	iium-538662017-07-18T06:07:20Z http://irep.iium.edu.my/53866/ Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies Ahmad Fuad, Fazia Adyani Houston, Douglas Robert Michels, Paul A M Fothergill- Gilmore, Linda A. Walkinshaw, Malcolm Douglas TA Engineering (General). Civil engineering (General) TA164 Bioengineering Cofactor-independent phosphoglycerate mutase has been proposed as a therapeutic target for the treatment of trypanosomatid diseases. In this paper, we report the identification of compounds that could potentially be developed as selective inhibitors of cofactor-independent phosphoglycerate mutase from Leishmania mexicana (LmiPGAM). Virtual screening was used in this search, as well as compounds identified by high-throughput screening. A ligand-based virtual screen programme, ultra fast shape recognition with atom types (UFSRAT), was used to screen for compounds resembling the substrate/product, before a structure-based approach was applied using AutoDock 4 and AutoDock Vina in a consensus docking scheme. In this way eight selected compounds were identified. In addition, three compounds from the Library of Pharmacologically Active Compounds (LOPAC) were selected from the published results of high-throughput screening of this library. The inhibitory effects of these compounds were tested at a fixed concentration of 1 mM. The results showed that seven compounds inhibited LmiPGAM activity and of these, two compounds (one each from high-throughput and virtual screening) showed substantial inhibition (i.e. 14% and 49% remaining activity, respectively). Taken together, the findings from this study indicate that these compounds have potential as novel inhibitors that specifically target LmiPGAM. Penerbit Universiti Kebangsaan Malaysia 2016-07 Article PeerReviewed application/pdf en http://irep.iium.edu.my/53866/1/53866_Inhibitors%20of%20Leishmania.pdf application/pdf en http://irep.iium.edu.my/53866/2/53866_Inhibitors%20of%20Leishmania_WOS.pdf application/pdf en http://irep.iium.edu.my/53866/4/53866_Inhibitors%20of%20Leishmania_SCOPUS.pdf Ahmad Fuad, Fazia Adyani and Houston, Douglas Robert and Michels, Paul A M and Fothergill- Gilmore, Linda A. and Walkinshaw, Malcolm Douglas (2016) Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies. Sains Malaysiana, 45 (7). pp. 1113-1120. ISSN 0126-6039 http://journalarticle.ukm.my/9986/1/14%20Fazia%20Adyani.pdf
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	TA Engineering (General). Civil engineering (General) TA164 Bioengineering
spellingShingle	TA Engineering (General). Civil engineering (General) TA164 Bioengineering Ahmad Fuad, Fazia Adyani Houston, Douglas Robert Michels, Paul A M Fothergill- Gilmore, Linda A. Walkinshaw, Malcolm Douglas Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
description	Cofactor-independent phosphoglycerate mutase has been proposed as a therapeutic target for the treatment of trypanosomatid diseases. In this paper, we report the identification of compounds that could potentially be developed as selective inhibitors of cofactor-independent phosphoglycerate mutase from Leishmania mexicana (LmiPGAM). Virtual screening was used in this search, as well as compounds identified by high-throughput screening. A ligand-based virtual screen programme, ultra fast shape recognition with atom types (UFSRAT), was used to screen for compounds resembling the substrate/product, before a structure-based approach was applied using AutoDock 4 and AutoDock Vina in a consensus docking scheme. In this way eight selected compounds were identified. In addition, three compounds from the Library of Pharmacologically Active Compounds (LOPAC) were selected from the published results of high-throughput screening of this library. The inhibitory effects of these compounds were tested at a fixed concentration of 1 mM. The results showed that seven compounds inhibited LmiPGAM activity and of these, two compounds (one each from high-throughput and virtual screening) showed substantial inhibition (i.e. 14% and 49% remaining activity, respectively). Taken together, the findings from this study indicate that these compounds have potential as novel inhibitors that specifically target LmiPGAM.
format	Article
author	Ahmad Fuad, Fazia Adyani Houston, Douglas Robert Michels, Paul A M Fothergill- Gilmore, Linda A. Walkinshaw, Malcolm Douglas
author_facet	Ahmad Fuad, Fazia Adyani Houston, Douglas Robert Michels, Paul A M Fothergill- Gilmore, Linda A. Walkinshaw, Malcolm Douglas
author_sort	Ahmad Fuad, Fazia Adyani
title	Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
title_short	Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
title_full	Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
title_fullStr	Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
title_full_unstemmed	Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
title_sort	inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
publisher	Penerbit Universiti Kebangsaan Malaysia
publishDate	2016
url	http://irep.iium.edu.my/53866/ http://irep.iium.edu.my/53866/ http://irep.iium.edu.my/53866/1/53866_Inhibitors%20of%20Leishmania.pdf http://irep.iium.edu.my/53866/2/53866_Inhibitors%20of%20Leishmania_WOS.pdf http://irep.iium.edu.my/53866/4/53866_Inhibitors%20of%20Leishmania_SCOPUS.pdf
first_indexed	2023-09-18T21:16:11Z
last_indexed	2023-09-18T21:16:11Z
_version_	1777411578407157760

Inhibitors of leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies

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