Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights
Renato B. Pereira,
Nuno F. S. Pinto,
Maria José G. Fernandes,
Tatiana F. Vieira,
Ana Rita O. Rodrigues,
David M. Pereira,
Sérgio F. Sousa,
Elisabete M. S. Castanheira,
A. Gil Fortes,
M. Sameiro T. Gonçalves
Affiliations
Renato B. Pereira
REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Nuno F. S. Pinto
Centre of Chemistry, Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
Maria José G. Fernandes
Centre of Chemistry, Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
Tatiana F. Vieira
Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Ana Rita O. Rodrigues
Centre of Physics of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
David M. Pereira
REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Sérgio F. Sousa
Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Elisabete M. S. Castanheira
Centre of Physics of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
A. Gil Fortes
Centre of Chemistry, Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
M. Sameiro T. Gonçalves
Centre of Chemistry, Department of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal
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.