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Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum

There is a continuous search for more reliable and effective alternatives to control phytopathogens through different strategies. In this context, indole-containing phytoalexins are stimuli-induced compounds implicated in plant defense against plant pathogens. However, phytoalexins’ efficacy have be...

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Autores principales: Angarita-Rodríguez, Andrea, Quiroga, Diego, Coy-Barrera, Ericsson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982726/
https://www.ncbi.nlm.nih.gov/pubmed/31877731
http://dx.doi.org/10.3390/molecules25010045
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author Angarita-Rodríguez, Andrea
Quiroga, Diego
Coy-Barrera, Ericsson
author_facet Angarita-Rodríguez, Andrea
Quiroga, Diego
Coy-Barrera, Ericsson
author_sort Angarita-Rodríguez, Andrea
collection PubMed
description There is a continuous search for more reliable and effective alternatives to control phytopathogens through different strategies. In this context, indole-containing phytoalexins are stimuli-induced compounds implicated in plant defense against plant pathogens. However, phytoalexins’ efficacy have been limited by fungal detoxifying mechanisms, thus, the research on bioisosteres-based analogs can be a friendly alternative regarding the control of Fusarium phytopathogens, but there are currently few studies on it. Thus, as part of our research on antifungal agents, a set of 21 synthetic indole-containing phytoalexin analogs were evaluated as inhibitors against the phyopathogen Fusarium oxysporum. Results indicated that analogs of the N,N-dialkylthiourea, N,S-dialkyldithiocarbamate and substituted-1,3-thiazolidin-5-one groups exhibited the best docking scores and interaction profiles within the active site of Fusarium spp. enzymes. Vina scores exhibited correlation with experimental mycelial growth inhibition using supervised statistics, and this antifungal dataset correlated with molecular interaction fields after CoMFA. Compound 24 (tert-butyl (((3-oxo-1,3-diphenylpropyl)thio)carbonothioyl)-l-tryptophanate), a very active analog against F. oxysporum, exhibited the best interaction with lanosterol 14α-demethylase according to molecular docking, molecular dynamics and molecular mechanic/poisson-boltzmann surface area (MM/PBSA) binding energy performance. After data analyses, information on mycelial growth inhibitors, structural requirements and putative enzyme targets may be used in further antifungal development based on phytoalexin analogs for controlling phytopathogens.
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spelling pubmed-69827262020-02-28 Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum Angarita-Rodríguez, Andrea Quiroga, Diego Coy-Barrera, Ericsson Molecules Article There is a continuous search for more reliable and effective alternatives to control phytopathogens through different strategies. In this context, indole-containing phytoalexins are stimuli-induced compounds implicated in plant defense against plant pathogens. However, phytoalexins’ efficacy have been limited by fungal detoxifying mechanisms, thus, the research on bioisosteres-based analogs can be a friendly alternative regarding the control of Fusarium phytopathogens, but there are currently few studies on it. Thus, as part of our research on antifungal agents, a set of 21 synthetic indole-containing phytoalexin analogs were evaluated as inhibitors against the phyopathogen Fusarium oxysporum. Results indicated that analogs of the N,N-dialkylthiourea, N,S-dialkyldithiocarbamate and substituted-1,3-thiazolidin-5-one groups exhibited the best docking scores and interaction profiles within the active site of Fusarium spp. enzymes. Vina scores exhibited correlation with experimental mycelial growth inhibition using supervised statistics, and this antifungal dataset correlated with molecular interaction fields after CoMFA. Compound 24 (tert-butyl (((3-oxo-1,3-diphenylpropyl)thio)carbonothioyl)-l-tryptophanate), a very active analog against F. oxysporum, exhibited the best interaction with lanosterol 14α-demethylase according to molecular docking, molecular dynamics and molecular mechanic/poisson-boltzmann surface area (MM/PBSA) binding energy performance. After data analyses, information on mycelial growth inhibitors, structural requirements and putative enzyme targets may be used in further antifungal development based on phytoalexin analogs for controlling phytopathogens. MDPI 2019-12-21 /pmc/articles/PMC6982726/ /pubmed/31877731 http://dx.doi.org/10.3390/molecules25010045 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Angarita-Rodríguez, Andrea
Quiroga, Diego
Coy-Barrera, Ericsson
Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum
title Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum
title_full Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum
title_fullStr Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum
title_full_unstemmed Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum
title_short Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum
title_sort indole-containing phytoalexin-based bioisosteres as antifungals: in vitro and in silico evaluation against fusarium oxysporum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982726/
https://www.ncbi.nlm.nih.gov/pubmed/31877731
http://dx.doi.org/10.3390/molecules25010045
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