Design, Synthesis, and Biological Evaluation of Pyrido [1,2-α] Pyrimidinone Mesoionic Derivatives Bearing Propenylbenzene as the Vector Control Insecticide.

Abstract

A series of novel pyrido [1,2-α] pyrimidinone mesoionic derivatives bearing a propenylbenzene group at the 1-position were synthesized on the basis of the structure of mesoionic insecticides triflumezopyrim and dicloromezotiaz via a rationally conceived pharmacophore model and evaluated for their insecticidal activities against three insect vectors. The bioassay results showed that some compounds exerted remarkable insecticidal activities against M. domestica, Ae. albopictus, and B. germanica. Particularly, compound 26l displayed outstanding insecticidal activity against Ae. Albopictus, with an LC50 value of 0.45 μg/mL, far superior to that of imidacloprid (LC50 = 1.82 μg/mL) and equivalent to that of triflumezopyrim (0.35 μg/mL). Meanwhile, compound 34l presented a broad insecticidal spectrum, with LC50 values of 1.51 μg/g sugar, 0.52 μg/mL and 0.14 μg/adult, which were about 2.88, 3.50, and 1.50 times better than that of imidacloprid (LC50 = 4.35 μg/g sugar, 1.82 μg/mL and 0.21 μg/adult against M. domestica, Ae. albopictus, and B. germanica, respectively) and equivalent to that of triflumezopyrim against M. domestica (1.13 μg/g sugar) and Ae. albopictus (0.35 μg/mL) but lower than the potency against B. germanica (0.06 μg/g sugar). The molecular docking study by energy minimizations revealed that introducing propenylbenzene at the 1-position of compounds 26l and 34l could embed into the binding pocket of nicotinic acetylcholine receptors and form pi-alkyl interaction with LEU306. These results demonstrated that compounds 26l and 34l could be promising candidates for vector control insecticides, which deserved further investigation.