Synthesis of Carlina Oxide Analogues and Evaluation of Their Insecticidal Efficacy and Cytotoxicity

Compoundsisolated from botanical sources represent innovativeand promising alternatives to conventional insecticides. Carlina oxideis a compound isolated from Carlina acaulis L. (Asteraceae)essential oil (EO) with great potential as bioinsecticide, being effectiveon various arthropod vectors and agricultural pests, with moderatetoxicity on non-target species. Since the production from the wildsource is limited, there is the need of exploring new synthetic routesfor obtaining this compound and analogues with improved bioactivityand lower toxicity. Herein, the chemical synthesis of carlina oxideanalogues was developed. Their insecticidal activity was assessedon the vectors Musca domestica L. and Culexquinquefasciatus Say, and their cytotoxicity was evaluatedon a human keratinocyte cell line (HaCaT). The compounds' activitywas compared with that of the natural counterparts EO and carlinaoxide. In housefly tests, the analogues were comparably effectiveto purified carlina oxide. In Cx. quinquefasciatus assays, the meta-chloro analogue provided a significantlyhigher efficacy (LC50 of 0.71 mu g mL(-1)) than the EO and carlina oxide (LC50 1.21 and 1.31 mu gmL(-1), respectively) and a better safety profilethan carlina oxide on keratinocytes. Overall, this study can openthe way to an agrochemical production of carlina oxide analogues employableas nature-inspired insecticides.