17‐ epi ‐Melianodiol, a new protolimonoid from Melia azedarach fruits, exhibits larvicidal activity and is associated with oxidative imbalance and midgut epithelial damage in Aedes aegypti larvae

BACKGROUND: In Brazil, Aedes aegypti is the primary vector of arboviruses such as dengue, chikungunya, yellow fever, and Zika virus, posing a major public health concern, particularly in underdeveloped regions where insecticide resistance and the circulation of highly virulent strains are increasing. In search of alternative and sustainable control strategies, this study evaluated the biolarvicidal potential of compounds from the fruits of Melia azedarach against third-instar Ae. aegypti larvae, focusing on larvicidal efficacy and associated physiological alterations. RESULTS: In this study, the crude methanolic extract caused 100% larval mortality at 100 ppm. After liquid-liquid partitioning, the dichloromethane fraction exhibited the highest larvicidal activity (86.0% mortality). Bioassay-guided fractionation led to the isolation of the new compound 17-epi-melianodiol (1), a protolimonoid, which showed relevant larvicidal activity (LC₅₀ = 41.5 ppm; LC₉₀ = 64.7 ppm). Larvae exposed to 1 displayed pronounced morphological alterations, including cuticular damage and extensive vacuolization, as revealed by optical and transmission electron microscopy. In addition, 1 significantly increased reactive oxygen species (ROS) levels in the larval midgut, indicating the occurrence of oxidative imbalance associated with tissue damage. CONCLUSIONS: In summary, these combined results suggest that 17-epi-melianodiol is a novel plant-derived larvicide with promising potential, contributing to our understanding of its physiological effects on Ae. aegypti larvae.