Harnessing carlina oxide scaffold for the management of vector-borne diseases: synthesis and structure–activity relationship

Abstract

Vector-borne diseases are causes of global health concern and mosquitoes are the primary transmitters of health-threatening pathogens. Botanicals are sources of compounds structurally modifiable into versatile hits for novel plant-based insecticides. Carlina oxide (1) is a natural compound isolated from Carlina acaulis L. (Asteraceae) with promising insecticidal potential, whose industrial production is limited by the absence of a plant supply chain. Herein, a one-step synthesis producing 1 in 81% yield was developed and a structure–activity relationship (SAR) study for the larvicidal activity on Aedes albopictus (Skuse, 1894) and Anopheles stephensi (Liston, 1901) was performed. The most promising analogue (5) displayed an encouraging larvicidal action (LC₅₀ < 6.0 μg mL⁻¹), safety profile on human keratinocytes (IC₅₀ > 100 μg mL⁻¹) and non-target organisms if compared to 1. Untargeted metabolomic analysis on mosquito larvae revealed that 1 and 5 target the carbohydrates and amino acid metabolism.