Synthesis, aphicidal activity and conformation of novel insect kinin analogues as potential eco-friendly insecticides.

Abstract

The discovery of ecofriendly insecticides through a new strategy for aphid control is important because of the substantial resistance and unexpected eco-toxicity to honeybees caused by traditional insecticides. The insect kinins, a class of multifunctional insect neuropeptides, are considered for potential application in pest control. In our previous work we developed several series of insect kinin analogues and found a promising lead II-1 with good aphicidal activity. To seek further eco-friendly aphicides, the optimization of II-1 is carried out in this study. Fifteen novel Yaa3 modified analogues based on the lead II-1 were synthesized. The aphicidal tests indicated that IV-3, IV-5 and IV-10 exhibited significant activity against the soybean aphid Aphis glycines with LC50 values of 0.0029, 0.0072 and 0.0086 mmol L-1 , respectively, higher than that of lead II-1 and the commercial Pymetrozine. The molecular modeling results showed that analogues II-1, IV-3, IV-5, IV-7 and IV-10 formed a β-turn-like conformation, while the conformation of analogues IV-1, IV-2 and IV-9 seemed to be linear. Some structural elements favorable for the activity were proposed based on the conformation-activity relationship of the analogues. Insect kinin analogues derived from lead II-1 by modifying the hydrolysis site Yaa3 with natural, sterically hindered α- and β-amino acids showed great potential as eco-friendly insecticides. Inspiringly, the most active analogue IV-3 can be a candidate for further development. The β-turn-like conformation and the orientation of the aromatic rings of the side chain of Phe2 and Trp4 may be critical factors beneficial to activity. © 2019 Society of Chemical Industry.