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

BACKGROUND: The discovery of ecofriendly insecticides through new strategy for aphid control is important because of the substantial resistance and unexpected eco-toxicity to honeybees caused by traditional insecticide. The insect kinins, a class of multifunctional insect neuropeptides, are considered for potential application in pest control. In our previous work, we have developed several series of insect kinin analogues and found a promising lead II-1 with good aphicidal activity. For the further discovery of eco-friendly aphicides, the further optimization on II-1 is carried out herein.
RESULTS: 15 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, 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 analysis of analogues conformation-activity relationship.
CONCLUSION: Insect kinins analogues derived from lead II-1 by modifying the hydrolysis site Yaa3 with natural, sterically hindered α- and β-amino acids showed great potency in the discovery of 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.