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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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 |
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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 |
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