Synthesis, Biological Activities And Target Study Of Novel Chlorantraniliprole Derivatives

The lepidopteran pests such as oriental armyworm are the harmful pests of crops in the world, which brings enormous losses in crop production. Chlorantraniliprole, an registered anthranilic diamide insecticide, shows high insecticidal activity to the lepidopteran pests, however with the drug resistance of pests as the large doses of pesticides using, a series of novel chlorantraniliprole derivatives were synthesized after structure modification.In order to identify novel chlorantraniliprole derivatives as potential insecticides or fungicides,25 analogues of chlorantraniliprole were synthesized. The insecticidal activities against oriental armyworm with Chlorantraniliprole, Avermectin and Indoxacarb as control and the antifungal activities against five typical fungi (Fusarium oxysporum, FO; Cercospora arachidicola, CA; Physalospora piricola, PP; Alternaria solani, AS and Fusarium graminearum, FG) of these derivatives were tested. Compounds 2u,2x and 2y exhibited good activities against oriental armyworm, especially compounds 2u and 2x which showed higher larvicidal activities than indoxacarb. Moreover, all of the tested compounds exhibited activities against five typical fungi.The Chlorantraniliprole acts by activating the insect ryanodine receptor, which is a calcium channel to affect calcium release from intracellular stores. Therefore, the ryanodine receptor has been regarded as one of the targets for novel insecticide discovery. However, the binding site action target of chlorantraniliprole on ryanodine receptor was uncertain; hence, the reasonable design of molecular structures could not achieved on the basis of target research.After we synthesis 25 novel chlorantraniliprole derivatives, the Chimera tool can be used to prepare molecules structures for docking calculations by adding hydrogens, assigning partial charges, and performing other related tasks. In our study, the membrane-spanning domain protein of the ryanodine receptor (GenBank accession No. JF927788) was selected as the possible specific receptor, which was proposed to bind with small molecules to give the Ki values using AutoDock4. The analysis of the relationship between the Ki values and the insecticidal activities against oriental armyworm could further indicated that the membrane-spanning domain protein (GenBank accession No. JF927788) of the ryanodine receptor might contain chlorantraniliprole binding sites.