Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights

Abstract

A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.

Eugenol β-Amino/β-Alkoxy Alcohols with Selective Anticancer Activity

“…& L.M. Perry through hydrodistillation, and then its epoxide 2 was prepared by reaction of eugenol 1 with m -chloroperoxybenzoic acid in dichloromethane using a known procedure [ 24 ].The reaction of eugenol epoxide 2 at 50 °C in ethanol and water with aniline, 4-cyanoaniline, octan-2-methylpropan-2-amine, 2-methylpropan-2-amine, 3-methoxyaniline, N -methylaniline, piperidine, and 3-bromoaniline, gave the eugenol β-amino alcohols 3 , 4 , 5 , 6 , 7 , 8 , 9 , and 14 , respectively, as we previously reported [ 25 ]. In addition, reaction of eugenol epoxide 2 , under nitrogen atmosphere, at 0 °C, using boron trifluoride diethyl etherate with ethanol, methanol, tert -butanol, and phenol afforded eugenol alkoxy alcohols 10 , 11 , 12 , and 13 , respectively ( Figure 8 ) [ 26 ].…”

Drug Repurposing Targeting Pseudomonas aeruginosa MvfR Using Docking, Virtual Screening, Molecular Dynamics, and Free-Energy Calculations

“…Four minimization steps were performed to remove clashed and applied in the following order: one water molecule (2500 steps); two hydrogens atoms (2500 steps); three side chains of all the amino acid residues (2500 steps); and four full systems (10,000 steps). After minimization, a molecular dynamics equilibration procedure was applied and divided into two stages: in the first stage (50 ps), the systems were gradually heated to 298 K using a Langevin thermostat at constant volume (NVT ensemble); in the second stage (50 ps), the density of the systems was further equilibrated at 298 K. Finally, the production phase was run for a total of 100 ns in an NPT ensemble at a pressure of 1 bar and a temperature of 298 K. This overall procedure has been previously used with success in the treatment of several biomolecular systems [ 72 , 73 , 74 , 75 ].…”

Spodoptera frugiperda Sf9 cells as a model system to investigate the role of detoxification gene expression in response to xenobiotics

“…Sf9 cells were derived from the ovary of the S. frugiperda pupa and have been used as a system for the heterologous expression of proteins for several decades ( Altmann et al., 1999 ; van Oers et al., 2015 ). However, they also have been employed to evaluate the potential of certain molecules to act as insecticides ( Pereira et al., 2021 ; Ruttanaphan et al., 2020 ). Indeed, Sf9 cells have been shown to be a useful model responsive to xenobiotics as well as to investigate potential resistance mechanisms ( Cui et al., 2020 ; Giraudo et al., 2011 , 2015 ; Saleh et al., 2013 ).…”