Synthesis and Insecticidal Activity of O -alkylated Oxirane Eugenol Derivatives

: The synthesis of three O -alkylated eugenol derivatives, bearing a hydroxypropyl chain and propyl esters, were synthesized and further converted into the corresponding oxiranes. Oxirane derivatives were then evaluated against their effect upon the viability of the insect cell line Sf9 ( Spodoptera frugiperda ), in comparison with the starting O -alkylates. The results pointing to their potential as bioinsecticides, with structural changes eliciting significant effects in terms of potency.


Introduction
In the last few decades, the need to prevent diseases and damage caused by the attack of various pests on plants has led to the application of high amounts of synthetic pesticides, including insecticides, which has resulted in the development of resistance to them by several harmful organisms [1]. As an alternative, natural products with insecticide activity have shown promise for insect control in agriculture [2,3]. The use of bioactive compounds of plants presents many advantages as insecticide, e.g., they are less hazardous to human and animal health, less expensive, non-toxic to non-target species, less resistant in the target organism, and are environmentally friendly [4]. Essential oils (EOs) exhibit antimicrobial activities with particular potential as insecticides [5]. Structural modifications in the constituents of EOs can further enhance their biocidal effect [2,4,6,7], being the best alternatives of synthetic chemicals and can be utilized as biopesticides or green pesticides [8][9][10].
Eugenol, the major component of clove oil, presents numerous applications, including in pharmaceutical, food and agricultural industries. It is an important insecticide that is widely efficient in a broad variety of domestic arthropod pests [6,11].
Considering all these facts, the synthesis of three O-alkylated eugenol derivatives and their respective oxiranes was carried out and then evaluated against the effect upon the viability of the insect cell line Sf9 (Spodoptera frugiperda), in comparison with the starting eugenol O-alkylates.

Toxicity of Eugenol Derivatives
In a general way, all molecules of the 1 and 2 series presented the same activity profile, namely, a mild toxic effect around 30-35% of viability reduction. The exception was 2c, which elicited a loss of around 50% of viability ( Figure 1). Considering that 2b and 2c present a rather similar structure, the only difference being the ester type, this feature seems to be of importance, given that the latter was more toxic than the former.

Viability Assessment
For the assessment of viability, a resazurin assay was used. Sf9 cells were plated at a density of 3.0 × 10 4 cells/well and incubated for 24 h with each molecule. After this period, a commercial solution of resazurin was added (1:10), and the kinetic reaction of fluorescence increase was monitored at 560/590 nm. We applied 60 min of incubation.

Conclusions
Three new O-alkylated eugenol derivatives, bearing a propyl chain with hydroxyl, methyl and ethyl esters as terminals and further converted into the corresponding oxiranes, were successfully synthetized.
We conducted an evaluation of all derivatives against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), and all molecules of the 1 and 2 series presented a mild toxic effect around 30-35% of viability reduction. Upon comparing all of the compounds, 2c exhibited a loss of around 50% of viability, presenting promising insecticidal activity.

Conflicts of Interest:
The authors declare no conflict of interest.