Cargando…

Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against A...

Descripción completa

Detalles Bibliográficos
Autores principales: da Silva Ramos, Ryan, da Silva Costa, Josivan, Campos Silva, Rai, Vilhena da Costa, Glauber, Bruno Lobato Rodrigues, Alex, de Menezes Rabelo, Érica, Nonato Picanço Souto, Raimundo, Anthony Taft, Carlton, Tomich de Paula da Silva, Carlos Henrique, Campos Rosa, Joaquín Maria, Rodrigues dos Santos, Cleydson Breno, da Cruz Macêdo, Williams Jorge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469432/
https://www.ncbi.nlm.nih.gov/pubmed/30691028
http://dx.doi.org/10.3390/ph12010020
_version_ 1783411641242615808
author da Silva Ramos, Ryan
da Silva Costa, Josivan
Campos Silva, Rai
Vilhena da Costa, Glauber
Bruno Lobato Rodrigues, Alex
de Menezes Rabelo, Érica
Nonato Picanço Souto, Raimundo
Anthony Taft, Carlton
Tomich de Paula da Silva, Carlos Henrique
Campos Rosa, Joaquín Maria
Rodrigues dos Santos, Cleydson Breno
da Cruz Macêdo, Williams Jorge
author_facet da Silva Ramos, Ryan
da Silva Costa, Josivan
Campos Silva, Rai
Vilhena da Costa, Glauber
Bruno Lobato Rodrigues, Alex
de Menezes Rabelo, Érica
Nonato Picanço Souto, Raimundo
Anthony Taft, Carlton
Tomich de Paula da Silva, Carlos Henrique
Campos Rosa, Joaquín Maria
Rodrigues dos Santos, Cleydson Breno
da Cruz Macêdo, Williams Jorge
author_sort da Silva Ramos, Ryan
collection PubMed
description Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD(50) values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of −10.5 and −10.3 kcal/mol, respectively. The interaction with the juvenile hormone was −11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.
format Online
Article
Text
id pubmed-6469432
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64694322019-04-24 Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening da Silva Ramos, Ryan da Silva Costa, Josivan Campos Silva, Rai Vilhena da Costa, Glauber Bruno Lobato Rodrigues, Alex de Menezes Rabelo, Érica Nonato Picanço Souto, Raimundo Anthony Taft, Carlton Tomich de Paula da Silva, Carlos Henrique Campos Rosa, Joaquín Maria Rodrigues dos Santos, Cleydson Breno da Cruz Macêdo, Williams Jorge Pharmaceuticals (Basel) Article Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD(50) values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of −10.5 and −10.3 kcal/mol, respectively. The interaction with the juvenile hormone was −11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents. MDPI 2019-01-25 /pmc/articles/PMC6469432/ /pubmed/30691028 http://dx.doi.org/10.3390/ph12010020 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
da Silva Ramos, Ryan
da Silva Costa, Josivan
Campos Silva, Rai
Vilhena da Costa, Glauber
Bruno Lobato Rodrigues, Alex
de Menezes Rabelo, Érica
Nonato Picanço Souto, Raimundo
Anthony Taft, Carlton
Tomich de Paula da Silva, Carlos Henrique
Campos Rosa, Joaquín Maria
Rodrigues dos Santos, Cleydson Breno
da Cruz Macêdo, Williams Jorge
Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening
title Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening
title_full Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening
title_fullStr Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening
title_full_unstemmed Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening
title_short Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening
title_sort identification of potential inhibitors from pyriproxyfen with insecticidal activity by virtual screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469432/
https://www.ncbi.nlm.nih.gov/pubmed/30691028
http://dx.doi.org/10.3390/ph12010020
work_keys_str_mv AT dasilvaramosryan identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT dasilvacostajosivan identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT campossilvarai identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT vilhenadacostaglauber identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT brunolobatorodriguesalex identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT demenezesrabeloerica identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT nonatopicancosoutoraimundo identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT anthonytaftcarlton identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT tomichdepauladasilvacarloshenrique identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT camposrosajoaquinmaria identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT rodriguesdossantoscleydsonbreno identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening
AT dacruzmacedowilliamsjorge identificationofpotentialinhibitorsfrompyriproxyfenwithinsecticidalactivitybyvirtualscreening