Synthesis, SAR, and in silico studies of new benzochromene derivatives as insecticidal agents against Culex pipiens L. larvae and adults

Mosquito control is a favorable strategy to prevent mosquito-borne diseases. There are various approaches for the management of potentially dreadful mosquito populations such as larvicides and adulticides. In this study, a series of novel benzochromene derivatives were synthesized and evaluated for their insecticidal efficacy against larvae and adult stages of Culex pipiens L. The synthesized compounds underwent comprehensive structural characterization and toxicological evaluation, revealing their larvicidal and adulticidal activity for several derivatives. The tested compounds were more effective against larvae than adults of C. pipiens. Compounds 10 and 5 exhibited pronounced larvicidal activity, surpassing the reference compound temephos, with LC₅₀ values of 40.15 and 46.17 ppm, respectively. In addition, both compounds displayed remarkable adulticidal efficacy, with LC₅₀ values of 55.02 and 65.43 ppm, respectively, whereas compound 6 showed the lowest potency among the tested series with LC₅₀ value of 215.40 ppm. Notably, compounds 10 and 5 were 5.36- and 4.66-fold more active against larvae than compound 6, and demonstrated 5.28- and 4.44-fold higher adulticidal efficiency compared with deltamethrin. In cytotoxicity assays, compound 5 displayed an IC₅₀ value of 72.65 µM, while compound 10 showed an IC₅₀ of 90.32 µM, indicating low toxicity toward normal human cells and a favorable selectivity index. Molecular docking supported this observation by demonstrating strong and specific binding interactions with Anopheles gambiae acetylcholinesterase (AChE). Additionally, the DFT results provided insights into the electronic properties and stability of the compounds, while MEP mapping highlighted key reactive sites associated with target interactions. Structure-activity relationship (SAR) studies identified crucial functional groups influencing insecticidal potency.