Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: A Repurposing Approach

Mohammed A. Khedr, Alberto Massarotti, Maged E. Mohamed

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

Lingua originaleInglese
Numero di articolo8565
RivistaScientific Reports
Volume8
Numero di pubblicazione1
DOI
Stato di pubblicazionePubblicato - 1 dic 2018

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