Identification of sulfonamide compounds active on the insect nervous system: Molecular modeling, synthesis and biological evaluation.

Autor: Selvam B; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France; Gossamer Bio, 3013 Science Park Road, Suite 200, San Diego, CA 92121, France., Landagaray E; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Cartereau A; Université d'Orléans, Laboratoire Biologie des Ligneux et des Grandes Cultures, USC INRAE 1328, Rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France., Laurent AD; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Graton J; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Lebreton J; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Thany SH; Université d'Orléans, Laboratoire Biologie des Ligneux et des Grandes Cultures, USC INRAE 1328, Rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France., Mathé-Allainmat M; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Le Questel JY; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France. Electronic address: Jean-Yves.Le-Questel@univ-nantes.fr.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2023 Jan 15; Vol. 80, pp. 129124. Date of Electronic Publication: 2023 Jan 04.
DOI: 10.1016/j.bmcl.2023.129124
Abstrakt: Insect nicotinic acetylcholine receptors (nAChRs) are a recognized target for insecticide design. In this work, we have identified, from a structure-based approach using molecular modeling tools, ligands with potential selective activity for pests versus pollinators. A high-throughput virtual screening with the Openeye software was performed using a library from the ZINC database, thiacloprid being used as the target structure. The top sixteen molecules were then docked in α6 cockroach and honeybee homomeric nAChRs to check from a theoretical point of view relevant descriptors in favor of pest selectivity. Among the selected molecules, one original sulfonamide compound has afterward been synthesized, together with various analogs. Two compounds of this family have been shown to behave as activators of the cockroach cholinergic synaptic transmission.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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