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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: Fazia Adyani Ahmad Fuad,, Houston, Douglas R., Michels, Paul A.M., Fothergill-Gillmore, Linda A., Walkinshaw, Malcolm D.
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2016
Online Access:http://journalarticle.ukm.my/9986/1/14%20Fazia%20Adyani.pdf
http://journalarticle.ukm.my/9986/
http://www.ukm.my/jsm/english_journals/vol45num7_2016/contentsVol45num7_2016.html
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spelling my-ukm.journal.99862017-01-20T00:54:43Z http://journalarticle.ukm.my/9986/ Inhibitors of Leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies Fazia Adyani Ahmad Fuad, Houston, Douglas R. Michels, Paul A.M. Fothergill-Gillmore, Linda A. Walkinshaw, Malcolm D. 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://journalarticle.ukm.my/9986/1/14%20Fazia%20Adyani.pdf Fazia Adyani Ahmad Fuad, and Houston, Douglas R. and Michels, Paul A.M. and Fothergill-Gillmore, Linda A. and Walkinshaw, Malcolm D. (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://www.ukm.my/jsm/english_journals/vol45num7_2016/contentsVol45num7_2016.html
institution Universiti Kebangsaan Malaysia
building Perpustakaan Tun Sri Lanang Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Kebangsaan Malaysia
content_source UKM Journal Article Repository
url_provider http://journalarticle.ukm.my/
language English
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 Fazia Adyani Ahmad Fuad,
Houston, Douglas R.
Michels, Paul A.M.
Fothergill-Gillmore, Linda A.
Walkinshaw, Malcolm D.
spellingShingle Fazia Adyani Ahmad Fuad,
Houston, Douglas R.
Michels, Paul A.M.
Fothergill-Gillmore, Linda A.
Walkinshaw, Malcolm D.
Inhibitors of Leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies
author_facet Fazia Adyani Ahmad Fuad,
Houston, Douglas R.
Michels, Paul A.M.
Fothergill-Gillmore, Linda A.
Walkinshaw, Malcolm D.
author_sort Fazia Adyani Ahmad Fuad,
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://journalarticle.ukm.my/9986/1/14%20Fazia%20Adyani.pdf
http://journalarticle.ukm.my/9986/
http://www.ukm.my/jsm/english_journals/vol45num7_2016/contentsVol45num7_2016.html
_version_ 1643737979023261696
score 13.211869

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