In vitro larvicidal activity of selected azabenzimidazole and diarylquinoline derivatives against Anopheles gambiae and in silico mechanistic analysis

Abstract

Different species of mosquitoes are responsible for transmitting infectious diseases such as chikungunya, dengue, Japanese encephalitis, lymphatic filariasis, rift valley fever, west nile fever, yellow fever, zika virus, and malaria. Particularly, malaria infection is endemic in sub-Saharan Africa region, and female anopheles mosquitoes is responsible for the transmission of the parasite causing the infection. The growing resistance of mosquitoes to conventional insecticides and the need to complement existing strategies for the elimination of malaria transmission necessitate the exploration of alternative vector control strategies. In this study, we investigated the in vitro larvicidal potential of three examples of diarylquinoline and two examples of azabenzimidazole derivatives against the fourth instar larvae of Anopheles gambiae. The compounds were also evaluated in silico, specifically targeting odorant-binding proteins (OBPs) of An. gambiae and Culex quinquefasciatus. The larvicidal assay indicated that three of the compounds exhibited significant bioactivity, with LC₅₀ below 20 µg/ml after 48 h. Molecular docking and dynamics simulations further elucidated the binding interactions between the active compounds and the selected OBPs, revealing high binding affinities and stable protein-ligand complexes. These findings suggest that two of the tested compounds have promising potential for optimization into larvicidal agents with OBPs inhibitory potential while complimenting existing mosquito control tools.

Keywords: Anopheles gambiae; Culex quinquefasciatus; Azabenzimidazole; Diarylquinoline; Odorant-binding protein.