AUTHOR=Iftikhar Sehrish , Shahid Ahmad A. , Halim Sobia A. , Wolters Pieter J. , Vleeshouwers Vivianne G. A. A. , Khan Ajmal , Al-Harrasi Ahmed , Ahmad Shahbaz 

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

JOURNAL=Frontiers in Chemistry

VOLUME=5

YEAR=2017

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2017.00100

DOI=10.3389/fchem.2017.00100

ISSN=2296-2646

ABSTRACT=<p><italic>Alternaria</italic> blight is an important foliage disease caused by <italic>Alternaria solani</italic>. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting <italic>Alternaria solani</italic> SDH enzyme could be efficient tool to design novel fungicides against <italic>A. solani</italic>. 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 <italic>in vitro</italic> and <italic>in vivo</italic>. The compounds were found to inhibit mycelial growth of <italic>A. solani</italic>. Moreover <italic>in vitro</italic> 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 <italic>in silico</italic> strategy led us to identify novel fungicides.</p>