Exploring the larvicidal and pupicidal activities of new functionalized pyridines against Culex pipiens L. referring to molecular docking and SAR studies

Abstract

Pesticides are intensively employed to manage pests, but they pose a great challenge, developing pesticide resistance. So, searching for novel chemical structures is crucial to overcoming insecticide resistance. Herein, a new functionalized pyridine derivative 4 was effectively constructed in a one-step reaction through reacting four components, including piperonal, ethyl cyanoacetate, 2-acetylthiophene, and ammonium acetate, under ultrasonic conditions. Treatment of the derivative 5 with hydrazine hydrate in ethanol afforded the acetohydrazide derivative 8 that was utilized as a key precursor for the synthesis of Schiff^'s bases and other nicotinonitriles. Moreover, new acetohydrazone derivatives (19–21) were furnished by the reaction of 8 with isatin, n-vinylpyrrolididone, and galactose, respectively. The data obtained from the spectral measurements was the basis for elucidating the structures of the new derivatives. The larvicidal and pupicidal potencies of the synthesized thienyl pyridine derivatives were assessed against Culex pipiens L., and most exhibited moderate to good activity. The larvae were more susceptible to 17, 19, 6 and 13 with LC₅₀ of 1.57, 1.91, 2.36 and 2.90 ppm, respectively, while pupae were less susceptible with LC₅₀ of 4.17, 5.03, 6.16 and 7.45 ppm, respectively. The various functional groups connected to the pyridine ring led to variations in the toxicity of synthesized compounds, which were clarified through the SAR study. At the same time, a molecular docking study was performed to demonstrate the compound's mode of action and the effect of inserted moieties on binding with the nicotinic acetylcholine receptors (nAChRs). Collectively, the results imply that the thienyl pyridine derivatives could be used as mosquitocidal agents against C. pipiens larvae and pupae.