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

Autor: Ramos RDS; Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, Amapá 68903-419, Brazil. ryanquimico@hotmail.com.; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. ryanquimico@hotmail.com.; Laboratory of Molecular Modeling and Simulation System, Federal Rural University of Amazônia, Capanema, Pará 68700-030, Brazil. ryanquimico@hotmail.com., Costa JDS; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. josivan.chemistry@gmail.com.; Laboratory of Molecular Modeling and Simulation System, Federal Rural University of Amazônia, Capanema, Pará 68700-030, Brazil. josivan.chemistry@gmail.com., Silva RC; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. camposchemistry@gmail.com.; Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, São Paulo 14040-903, Brazil;. camposchemistry@gmail.com., da Costa GV; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. vilhenac@hotmail.com., Rodrigues ABL; Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, Amapá 68903-419, Brazil. alexrodrigues.quim@gmail.com.; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. alexrodrigues.quim@gmail.com., Rabelo ÉM; Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, Amapá 68903-419, Brazil. ericamrabelo@gmail.com., Souto RNP; Laboratory of Arthropoda, Federal University of Amapá, Macapá 68902-280, AP, Brazil. nonatoiepa@hotmail.com., Taft CA; Brazilian Center for Physical Research, Urca, Rio de Janeiro 22290-180, Brazil. catff@terra.com.br., Silva CHTPD; Laboratory of Molecular Modeling and Simulation System, Federal Rural University of Amazônia, Capanema, Pará 68700-030, Brazil. tomich@fcfrp.usp.br.; Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, São Paulo 14040-903, Brazil;. tomich@fcfrp.usp.br., Rosa JMC; Department of Pharmaceutical Organic Chemistry, University of Granada, 18071 Granada, Spain. jmcampos@ugr.es., Santos CBRD; Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, Amapá 68903-419, Brazil. breno@unifap.br.; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. breno@unifap.br.; Computational Laboratory of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, São Paulo 14040-903, Brazil;. breno@unifap.br., Macêdo WJDC; Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, Amapá 68903-419, Brazil. williamsmacedo@yahoo.com.br.; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. williamsmacedo@yahoo.com.br.; Laboratory of Molecular Modeling and Simulation System, Federal Rural University of Amazônia, Capanema, Pará 68700-030, Brazil. williamsmacedo@yahoo.com.br.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2019 Jan 25; Vol. 12 (1). Date of Electronic Publication: 2019 Jan 25.
DOI: 10.3390/ph12010020
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje