TY - JOUR
T1 - Ligand-based virtual screening, molecular docking, and molecular dynamics of eugenol analogs as potential acetylcholinesterase inhibitors with biological activity against Spodoptera frugiperda
AU - Méndez-Álvarez, Domingo
AU - Herrera-Mayorga, Verónica
AU - Juárez-Saldivar, Alfredo
AU - Paz-González, Alma D.
AU - Ortiz-Pérez, Eyra
AU - Bandyopadhyay, Debasish
AU - Pérez-Sánchez, Horacio
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PY - 2022/8
Y1 - 2022/8
N2 - The development of new, more selective, environmental-friendly insecticide alternatives is in high demand for the control of Spodoptera frugiperda (S. frugiperda). The major objective of this work was to search for new potential S. frugiperda acetylcholinesterase (AChE) inhibitors. A ligand-based virtual screening was initially carried out considering six scaffolds derived from eugenol and the ZINC15, PubChem, and MolPort databases. Subsequently, molecular docking analysis of the selected compounds on the active site and a second region (determined by blind molecular docking) of the AChE of S. frugiperda was performed. Molecular dynamics and Molecular Mechanics Poisson–Boltzmann Surface Area analyses were also applied to improve the docking results. Finally, three new eugenol analogs were evaluated in vitro against S. frugiperda larvae. The virtual screening identified 1609 compounds from the chemical libraries. Control compounds were selected from the interaction fingerprint by molecular docking. Only three new eugenol analogs (1, 3, and 4) were stable at 50 ns by molecular dynamics. Compounds 1 and 4 had the best biological activity by diet (LC50 = 0.042 mg/mL) and by topical route (LC50 = 0.027 mg/mL), respectively. At least three new eugenol derivatives possessed good-to-excellent insecticidal activity against S. frugiperda. Graphic abstract: [Figure not available: see fulltext.].
AB - The development of new, more selective, environmental-friendly insecticide alternatives is in high demand for the control of Spodoptera frugiperda (S. frugiperda). The major objective of this work was to search for new potential S. frugiperda acetylcholinesterase (AChE) inhibitors. A ligand-based virtual screening was initially carried out considering six scaffolds derived from eugenol and the ZINC15, PubChem, and MolPort databases. Subsequently, molecular docking analysis of the selected compounds on the active site and a second region (determined by blind molecular docking) of the AChE of S. frugiperda was performed. Molecular dynamics and Molecular Mechanics Poisson–Boltzmann Surface Area analyses were also applied to improve the docking results. Finally, three new eugenol analogs were evaluated in vitro against S. frugiperda larvae. The virtual screening identified 1609 compounds from the chemical libraries. Control compounds were selected from the interaction fingerprint by molecular docking. Only three new eugenol analogs (1, 3, and 4) were stable at 50 ns by molecular dynamics. Compounds 1 and 4 had the best biological activity by diet (LC50 = 0.042 mg/mL) and by topical route (LC50 = 0.027 mg/mL), respectively. At least three new eugenol derivatives possessed good-to-excellent insecticidal activity against S. frugiperda. Graphic abstract: [Figure not available: see fulltext.].
KW - Eugenol
KW - Interaction fingerprint
KW - Molecular docking
KW - Molecular dynamics
UR - http://www.scopus.com/inward/record.url?scp=85115052550&partnerID=8YFLogxK
U2 - 10.1007/s11030-021-10312-5
DO - 10.1007/s11030-021-10312-5
M3 - Artículo
C2 - 34529209
AN - SCOPUS:85115052550
SN - 1381-1991
VL - 26
SP - 2025
EP - 2037
JO - Molecular Diversity
JF - Molecular Diversity
IS - 4
ER -