Insect kinin mimics act as potential control agents for aphids: Structural modifications of Trp⁴

Insect kinins are endogenous, biologically active peptides with various physiological functions. The use of insect kinins in plant protection is being evaluated by many groups. Some kinins have been chosen as lead compounds for pest control. We previously reported an insect kinin mimic IV-3 that had insecticidal activity. And by introducing a strong electron withdrawing group (-CF3) on the benzene ring (Phe(2)), we discovered a compound, L-7, with better activity than lead IV-3. In this work, taking L-7 as the lead compound, we designed and synthesized 13 compounds to evaluate the influence of position 4 (Trp(4)) of insect kinin on insecticidal activity, by replacing the H atom on tryptophan with -CH3 and -Cl or substituting the indole ring of tryptophan with the benzene, naphthalene, pyridine, imidazole, cyclohexane, and alkyl carboxamides. The aphid bioassay results showed that the compounds M-1, M-3, and M-5 were more active than the positive control, pymetrozine. Especially, replacing the side chain by an indole ring with 4-Cl substitution (M-1, LC50 = 0.0029 mmol/L) increased the aphicidal activity. The structure-activity relationships (SARs) indicated that the side chain benzene ring at this position may be important to the aphicidal activity. In addition, the toxicity prediction by Toxtree, and the toxicity experiments on Apis mellifera suggested that M-1 was no toxicity risk on a non-target organism. It could be used as a selective and bee-friendly insecticide to control aphids.