Chemical structure-biological activity of 1,4-naphthoquinone analogs as potential Aedes aegypti larvicides

1,4-Naphthoquinone compounds have shown pesticidal activity against Aedes aegypti larvae, a key vector of diseases such as dengue and Zika. However, limited knowledge of their structure-activity relationships has hindered their optimization for pesticide development. This study investigates the structure-activity relationships of 1,4-naphthoquinone, particularly 2-hydroxy-1,4-naphthoquinone and its derivatives.

A series of 1,4-naphthoquinones with modifications at the C-2, C-5, and C-8 positions were synthesized and tested for larvicidal activities against Ae. aegypti. The presence of chlorine substituents at the C-2 position significantly increased mosquito larval mortality. In contrast, 2-hydroxy and 2-methoxy groups were less effective, highlighting the importance of the C-2 substituent in determining larvicidal activity. The compounds were tested on both pyrethroid-susceptible Orlando 1952 (ORL1952) and permethrin-resistant Puerto Rico (PR) strains of Ae. aegypti. While compound 1d exhibited the lowest median lethal concentration (LC₅₀) against ORL1952 larvae, it showed minimal activity against the PR strain, which is resistant. The most promising compounds, 1 and 4a, showed LC₅₀ values of 2.764 and 4.916 ppm in the ORL strain, and 2.548 and 4.878 ppm in the PR strain, respectively.

Chlorine substitution at the C-2 position of 1,4-naphthoquinones enhances larvicidal activity against Ae. aegypti, while 2-hydroxy and 2-methoxy substitutions reduce efficacy. Certain compounds, such as 1 and 4a, show potential as broad-spectrum agents effective against both susceptible and resistant strains of Ae. aegypti, highlighting their promise for further development as mosquito control agents. © 2025 Society of Chemical Industry.