Synthesis, computational and nanoencapsulation studies on eugenol-derived insecticides

A new set of alkoxy alcohols were synthesised by reaction of eugenol oxirane with aliphatic and aromatic alcohols. These eugenol derivatives were evaluated against their effect upon the viability of the insect cell line Sf9 (Spodoptera frugiperda). The most promising compounds, 4-(3-(tert-butoxy)-2-hydroxypropyl)-2-methoxyphenol and 4-(2-((4-fluorobenzyl)oxy)-3-hydroxypropyl)-2-methoxyphenol were submitted to in silico assays to predict possible targets. Throught an Inverted Virtual Screening approach, 23 common pesticide targets were screened and the top 2 targets predicted were further analyzed through molecular dynamics simulations and free energy calculations. In addition, these eugenol derivatives were subjected to encapsulation and release assays using liposome-based nanosystems of egg phosphatidylcholine/cholesterol (7:3), with encapsulation efficiencies higher than 90% and release profiles well described by both Korsmeyer-Peppas and Weibull models.This research was funded by the project PTDC/ASP-AGR/30154/2017 (POCI-01-0145-FEDER-030154) of the COMPETE 2020 program, co-financed by the FEDER and the European Union. The authors also acknowledge the Foundation for Science and Technology (FCT, Portugal) and FEDERCOMPETE-QREN-EU for financial support to the research centers CQ-UM (UID/QUI/00686/2021), CF-UM-UP (UIDB/04650/2021) and REQUIMTE (UIDB/50006/2020). Renato B. Pereira acknowledges the PRIMA Foundation (H2020-PRIMA 2018-Section 2, Project MILKQUA) and FCT (PTDC/QUI-QFI/2870/2020) for the funding. The NMR spectrometer Bruker Avance III 400 was a part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT