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

Authors: Kim, Seong Jong; KHAN, IMDADUL - University Of Mississippi; Estep Iii, Alden; Cantrell, Charles; LE, HOANG - National Institutes Of Health (NIH)

Submitted to: Pest Management Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Mosquitoes, notably Aedes aegypti (L.) (Diptera: Culicidae), are key vectors responsible for transmitting various severe viral infections, including dengue, yellow fever, chikungunya, Zika viruses, and potentially the Venezuelan Equine Encephalitis and West Nile viruses. Historically, synthetic insecticides have been relied upon to control mosquito larvae populations. However, the emergence of resistance to commonly used insecticides has posed a significant challenge, necessitating the exploration of novel agents with distinct modes of action. Plant-derived compounds have garnered attention due to their rich repository of biologically active substances. Among these, 1,4-naphthoquinones constitute a diverse group of natural products found in several plants (Juglans regia, Arnebia euchroma, and Plumbago zeylanica), fungi and bacteria. However, limited information has hindered the optimization of their structures and formulations as pesticides. This study delves into a comprehensive structure-activity relationship (SAR) analysis of naphthoquinone. Certain compounds produced from this study show potential as broad-spectrum agents effective against both susceptible and resistant strains of Aedes aegypti, highlighting their promise for further development as mosquito control agents.

Technical Abstract: The 1,4-naphthoquinone class and structurally related compounds have exhibited pesticide activity against Ae. aegypti larvae; however, limited information has hindered the optimization of their structures and formulations as pesticides. This study examines 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 positions C-2, C-5, and C-8 are reported along with their mosquito larvicidal activity against Aedes aegypti. The presence of chlorine substituents at the C-2 position significantly augmented mosquito larval mortality. 2-hydroxy and 2-methoxy substituted groups exhibited diminished efficacy compared to 2-chloro derivatives, underscoring the significance of the C-2 substituent. The series of compounds were also evaluated for activity against larvae of both the ORL 1952 and PR strains of Ae. aegypti. Compound 1d, boasting the lowest LC50 for ORL1952 larvae, displayed negligible activity against the resistant PR strain. Conversely, compounds 1 and 4a exhibited promising efficacy against both strains.