Synthesis, molecular docking studies, and larvicidal activity evaluation of new fluorinated neonicotinoids against Anopheles darlingi larvae

Abstract

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 3 rd 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-1ylmethyl)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.

Extracts of Euphorbia nivulia Buch.-Ham. showed both phytotoxic and insecticidal capacities against Lemna minor L. and Oxycarenus hyalinipennis Costa

“…A control treatment was maintained by applying water spray. The treatments were triplicated under laboratory conditions (25±1°C, 65±5% RH) [ 29 ].…”

Insecticidal activity of essential oils from American native plants against Aedes aegypti (Diptera: Culicidae): an introduction to their possible mechanism of action

“…When searching for components to design green insecticides, it is crucial to have a primary approximation of their compounds and how they contribute to the synergy of the biocidal effect. For this, computational approaches have become pivotal tools for bioactive compound identification for insecticide formulation 10 . Structure-based virtual screening (SBVS) is probably the most widely used in the lead compound identification in biological assays; however, this computational approach has some limitations related to the compounds library quality that has an important effect on SBVS results as well as on the use of the rule-of-five including molecular weight (MW), LogP, H-donors, H-acceptors, and different physicochemical filters for the library 11 .…”

Design, Synthesis, in vitro and in silico Characterization of 2‐Quinolone‐L‐alaninate‐1,2,3‐triazoles as Antimicrobial Agents

“…For example, quinolone antibiotics represent one of the compound classes whose use has been compromised by the increasing emergence of resistant strains [2] . Currently many research groups are working on the design of new antimicrobial drugs and, namely, design of molecules containing heterocyclic rings, which is encouraged by the fact that such molecules have been shown to exhibit a wide range of biological activities [3–10] …”

“… [2] Currently many research groups are working on the design of new antimicrobial drugs and, namely, design of molecules containing heterocyclic rings, which is encouraged by the fact that such molecules have been shown to exhibit a wide range of biological activities. [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]…”