Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional do INPA |
Texto Completo: | https://repositorio.inpa.gov.br/handle/1/14640 |
Resumo: | Anopheles darlingi is the main vector of malaria in Brazil, characterized by a high level of anthropophilia and endophagy. Imidacloprid, thiacloprid, and acetamiprid are the most widespread insecticides of the neonicotinoid group. However, they produce adverse effects on the non-target insects. Flupyradifurone has been marketed as an alternative to non-fluorinated neonicotinoids. Neonicotinoids containing trifluoroacethyl substituent reveal increased insecticidal activity due to higher hydrophobicity and metabolic stability. We synthesized novel neonicotinoid insecticides containing fluorinated acceptor groups and their interactions were estimated with the nicotinic acetylcholine receptor (nAChR) binding site by molecular docking studies, to evaluate their larvicidal activity against A. darlingi, and to assess their outdoor photodegradation behavior. New neonicotinoid analogues were prepared and characterized by NMR and mass-spectrometry. The synthesized molecules were modelled by time-dependent density functional theory and analyzed, their interaction with nAChR was investigated by molecular docking. Their insecticide activity was tested on Anopheles larvae collected in suburban area of Manaus, Brazil. Four new fluorinated neonicotinoid analogs were prepared and tested against 3rd instars larvae of A. darlingi showing high larvicidal activity. Docking studies reveal binding modes of the synthesized compounds and suggest that their insecticidal potency is governed by specific interactions with the receptor binding site and enhanced lipophilicity. 2-Chloro-5-(2-trifluoromethyl-pyrrolidin-1-ylmethyl)pyridine 5 showed fast degradation in water maintaining high larvicidal activity. All obtained substances possessed high larvicidal activity in low concentrations in 48 hours of exposure, compared to commercial flupyradifurone. Such activity is connected to a unique binding pattern of the synthesized compounds to insect's nAChR and to their enhanced bioavailability owing to introduction of fluorinated amino-moieties. Therefore, the compounds in question have a high potential for application as control agents for insects transmitting tropical diseases, and they will be less persistent in the environment. © 2020 da Silva Mesquita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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Mesquita, Rochelly da SilvaKyrylchuk, AndriiGrafova, Iryna A.Kliukovskyi, DenysBezdudny, Andriy V.Rozhenko, Alexander B.Tadei, Wanderli PedroLeskelä, Markku A.Grafov, Andrèi Andriy2020-04-24T16:59:51Z2020-04-24T16:59:51Z2020https://repositorio.inpa.gov.br/handle/1/1464010.1371/journal.pone.0227811Anopheles darlingi is the main vector of malaria in Brazil, characterized by a high level of anthropophilia and endophagy. Imidacloprid, thiacloprid, and acetamiprid are the most widespread insecticides of the neonicotinoid group. However, they produce adverse effects on the non-target insects. Flupyradifurone has been marketed as an alternative to non-fluorinated neonicotinoids. Neonicotinoids containing trifluoroacethyl substituent reveal increased insecticidal activity due to higher hydrophobicity and metabolic stability. We synthesized novel neonicotinoid insecticides containing fluorinated acceptor groups and their interactions were estimated with the nicotinic acetylcholine receptor (nAChR) binding site by molecular docking studies, to evaluate their larvicidal activity against A. darlingi, and to assess their outdoor photodegradation behavior. New neonicotinoid analogues were prepared and characterized by NMR and mass-spectrometry. The synthesized molecules were modelled by time-dependent density functional theory and analyzed, their interaction with nAChR was investigated by molecular docking. Their insecticide activity was tested on Anopheles larvae collected in suburban area of Manaus, Brazil. Four new fluorinated neonicotinoid analogs were prepared and tested against 3rd instars larvae of A. darlingi showing high larvicidal activity. Docking studies reveal binding modes of the synthesized compounds and suggest that their insecticidal potency is governed by specific interactions with the receptor binding site and enhanced lipophilicity. 2-Chloro-5-(2-trifluoromethyl-pyrrolidin-1-ylmethyl)pyridine 5 showed fast degradation in water maintaining high larvicidal activity. All obtained substances possessed high larvicidal activity in low concentrations in 48 hours of exposure, compared to commercial flupyradifurone. Such activity is connected to a unique binding pattern of the synthesized compounds to insect's nAChR and to their enhanced bioavailability owing to introduction of fluorinated amino-moieties. Therefore, the compounds in question have a high potential for application as control agents for insects transmitting tropical diseases, and they will be less persistent in the environment. © 2020 da Silva Mesquita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Volume 15, Número 2Attribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccess2 Chloro 5 (2 Trifluoromethylpyrrolidin 1 Ylmethyl)pyridineFlupyradifuroneN [(6 Chloropyridin 3 Yl)methyl] 3 (trifluoromethyl)anilineN [(6 Chloropyridin 3 Yl)methyl] 3,5 Bis(trifluoromethyl)anilineN [(6 Chloropyridin 3 Yl)methyl] 4 (pentafluoroethoxy)anilineNeonicotinoidNicotinic ReceptorUnclassified DrugAnopheles DarlingiBinding SiteBrasilChemical StructureControlled StudyInsect LarvaLarvicidal ActivityLipophilicityMolecular DockingNonhumanPhotodegradationReceptor BindingSynthesisSynthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvaeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlePLoS ONEengreponame:Repositório Institucional do INPAinstname:Instituto Nacional de Pesquisas da Amazônia (INPA)instacron:INPAORIGINALartigo-inpa.pdfapplication/pdf2194801https://repositorio.inpa.gov.br/bitstream/1/14640/1/artigo-inpa.pdf31e9aac168e7a8ad457fde23dca0c421MD51CC-LICENSElicense_rdfapplication/octet-stream914https://repositorio.inpa.gov.br/bitstream/1/14640/2/license_rdf4d2950bda3d176f570a9f8b328dfbbefMD521/146402020-07-14 09:18:18.319oai:repositorio:1/14640Repositório de PublicaçõesPUBhttps://repositorio.inpa.gov.br/oai/requestopendoar:2020-07-14T13:18:18Repositório Institucional do INPA - Instituto Nacional de Pesquisas da Amazônia (INPA)false |
dc.title.en.fl_str_mv |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
title |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
spellingShingle |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae Mesquita, Rochelly da Silva 2 Chloro 5 (2 Trifluoromethylpyrrolidin 1 Ylmethyl)pyridine Flupyradifurone N [(6 Chloropyridin 3 Yl)methyl] 3 (trifluoromethyl)aniline N [(6 Chloropyridin 3 Yl)methyl] 3,5 Bis(trifluoromethyl)aniline N [(6 Chloropyridin 3 Yl)methyl] 4 (pentafluoroethoxy)aniline Neonicotinoid Nicotinic Receptor Unclassified Drug Anopheles Darlingi Binding Site Brasil Chemical Structure Controlled Study Insect Larva Larvicidal Activity Lipophilicity Molecular Docking Nonhuman Photodegradation Receptor Binding Synthesis |
title_short |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
title_full |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
title_fullStr |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
title_full_unstemmed |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
title_sort |
Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae |
author |
Mesquita, Rochelly da Silva |
author_facet |
Mesquita, Rochelly da Silva Kyrylchuk, Andrii Grafova, Iryna A. Kliukovskyi, Denys Bezdudny, Andriy V. Rozhenko, Alexander B. Tadei, Wanderli Pedro Leskelä, Markku A. Grafov, Andrèi Andriy |
author_role |
author |
author2 |
Kyrylchuk, Andrii Grafova, Iryna A. Kliukovskyi, Denys Bezdudny, Andriy V. Rozhenko, Alexander B. Tadei, Wanderli Pedro Leskelä, Markku A. Grafov, Andrèi Andriy |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Mesquita, Rochelly da Silva Kyrylchuk, Andrii Grafova, Iryna A. Kliukovskyi, Denys Bezdudny, Andriy V. Rozhenko, Alexander B. Tadei, Wanderli Pedro Leskelä, Markku A. Grafov, Andrèi Andriy |
dc.subject.eng.fl_str_mv |
2 Chloro 5 (2 Trifluoromethylpyrrolidin 1 Ylmethyl)pyridine Flupyradifurone N [(6 Chloropyridin 3 Yl)methyl] 3 (trifluoromethyl)aniline N [(6 Chloropyridin 3 Yl)methyl] 3,5 Bis(trifluoromethyl)aniline N [(6 Chloropyridin 3 Yl)methyl] 4 (pentafluoroethoxy)aniline Neonicotinoid Nicotinic Receptor Unclassified Drug Anopheles Darlingi Binding Site Brasil Chemical Structure Controlled Study Insect Larva Larvicidal Activity Lipophilicity Molecular Docking Nonhuman Photodegradation Receptor Binding Synthesis |
topic |
2 Chloro 5 (2 Trifluoromethylpyrrolidin 1 Ylmethyl)pyridine Flupyradifurone N [(6 Chloropyridin 3 Yl)methyl] 3 (trifluoromethyl)aniline N [(6 Chloropyridin 3 Yl)methyl] 3,5 Bis(trifluoromethyl)aniline N [(6 Chloropyridin 3 Yl)methyl] 4 (pentafluoroethoxy)aniline Neonicotinoid Nicotinic Receptor Unclassified Drug Anopheles Darlingi Binding Site Brasil Chemical Structure Controlled Study Insect Larva Larvicidal Activity Lipophilicity Molecular Docking Nonhuman Photodegradation Receptor Binding Synthesis |
description |
Anopheles darlingi is the main vector of malaria in Brazil, characterized by a high level of anthropophilia and endophagy. Imidacloprid, thiacloprid, and acetamiprid are the most widespread insecticides of the neonicotinoid group. However, they produce adverse effects on the non-target insects. Flupyradifurone has been marketed as an alternative to non-fluorinated neonicotinoids. Neonicotinoids containing trifluoroacethyl substituent reveal increased insecticidal activity due to higher hydrophobicity and metabolic stability. We synthesized novel neonicotinoid insecticides containing fluorinated acceptor groups and their interactions were estimated with the nicotinic acetylcholine receptor (nAChR) binding site by molecular docking studies, to evaluate their larvicidal activity against A. darlingi, and to assess their outdoor photodegradation behavior. New neonicotinoid analogues were prepared and characterized by NMR and mass-spectrometry. The synthesized molecules were modelled by time-dependent density functional theory and analyzed, their interaction with nAChR was investigated by molecular docking. Their insecticide activity was tested on Anopheles larvae collected in suburban area of Manaus, Brazil. Four new fluorinated neonicotinoid analogs were prepared and tested against 3rd instars larvae of A. darlingi showing high larvicidal activity. Docking studies reveal binding modes of the synthesized compounds and suggest that their insecticidal potency is governed by specific interactions with the receptor binding site and enhanced lipophilicity. 2-Chloro-5-(2-trifluoromethyl-pyrrolidin-1-ylmethyl)pyridine 5 showed fast degradation in water maintaining high larvicidal activity. All obtained substances possessed high larvicidal activity in low concentrations in 48 hours of exposure, compared to commercial flupyradifurone. Such activity is connected to a unique binding pattern of the synthesized compounds to insect's nAChR and to their enhanced bioavailability owing to introduction of fluorinated amino-moieties. Therefore, the compounds in question have a high potential for application as control agents for insects transmitting tropical diseases, and they will be less persistent in the environment. © 2020 da Silva Mesquita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-04-24T16:59:51Z |
dc.date.available.fl_str_mv |
2020-04-24T16:59:51Z |
dc.date.issued.fl_str_mv |
2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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https://repositorio.inpa.gov.br/handle/1/14640 |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0227811 |
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https://repositorio.inpa.gov.br/handle/1/14640 |
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10.1371/journal.pone.0227811 |
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eng |
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eng |
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Volume 15, Número 2 |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ |
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openAccess |
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PLoS ONE |
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PLoS ONE |
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