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Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight

Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against...

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Autores principales: Iftikhar, Sehrish, Shahid, Ahmad A., Halim, Sobia A., Wolters, Pieter J., Vleeshouwers, Vivianne G. A. A., Khan, Ajmal, Al-Harrasi, Ahmed, Ahmad, Shahbaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698277/
https://www.ncbi.nlm.nih.gov/pubmed/29204422
http://dx.doi.org/10.3389/fchem.2017.00100
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author Iftikhar, Sehrish
Shahid, Ahmad A.
Halim, Sobia A.
Wolters, Pieter J.
Vleeshouwers, Vivianne G. A. A.
Khan, Ajmal
Al-Harrasi, Ahmed
Ahmad, Shahbaz
author_facet Iftikhar, Sehrish
Shahid, Ahmad A.
Halim, Sobia A.
Wolters, Pieter J.
Vleeshouwers, Vivianne G. A. A.
Khan, Ajmal
Al-Harrasi, Ahmed
Ahmad, Shahbaz
author_sort Iftikhar, Sehrish
collection PubMed
description Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides.
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spelling pubmed-56982772017-12-04 Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight Iftikhar, Sehrish Shahid, Ahmad A. Halim, Sobia A. Wolters, Pieter J. Vleeshouwers, Vivianne G. A. A. Khan, Ajmal Al-Harrasi, Ahmed Ahmad, Shahbaz Front Chem Chemistry Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides. Frontiers Media S.A. 2017-11-17 /pmc/articles/PMC5698277/ /pubmed/29204422 http://dx.doi.org/10.3389/fchem.2017.00100 Text en Copyright © 2017 Iftikhar, Shahid, Halim, Wolters, Vleeshouwers, Khan, Al-Harrasi and Ahmad. 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.
spellingShingle Chemistry
Iftikhar, Sehrish
Shahid, Ahmad A.
Halim, Sobia A.
Wolters, Pieter J.
Vleeshouwers, Vivianne G. A. A.
Khan, Ajmal
Al-Harrasi, Ahmed
Ahmad, Shahbaz
Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight
title Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight
title_full Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight
title_fullStr Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight
title_full_unstemmed Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight
title_short Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight
title_sort discovering novel alternaria solani succinate dehydrogenase inhibitors by in silico modeling and virtual screening strategies to combat early blight
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698277/
https://www.ncbi.nlm.nih.gov/pubmed/29204422
http://dx.doi.org/10.3389/fchem.2017.00100
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