Screening,Sythesis And Activity Study Of Sorbitol Dehydrogenase Inhibitor

Lepidoptera insects are holometabolous insects.During the larval stage,many lepidoptera insects feed on the roots of plants,which brings great threat to crop production.This problem needs us to take effect measures to control the growth process of lepidoptera insects.The diapause process of lepidoptera insects occurs at a certain stage of individual development,before the adverse environment arrives,which is caused by some seasonal signals,such as light cycle or temperature change.Lepidoptera insects can enter into the diapause state at different periods,and the hormone level changes in the diapause condition.Sorbitol dehudrogenase is a key enzyme in the conversion of sorbitol into glycongen in the hormone regulation mechanism of diapause.Sorbitol dehydrogenase(SDH)is widely found in plants and animals.In the polyol metabolism pathway,the oxidation of Sorbitol to glycogen is used to provide energy for the body.Sorbitol as main energy in the process of metabolism of insect material,widely exists in many insects,such as Artemia sinica and Bombyx mori L.During their embryo diapause,they can accumulate amount of sorbitol protecting embryo survival in low temperature environment.Antherea pernyi is a kind of lepidoptera insects which have their diapause pupae.The changes of sorbitol content in pupae are closely related to the beginning,persistence and cessation of pupal diapause.Therefore,if the activity of SDH can be inhibited in vitro,it will be expected to interfere with the metabolic process of sorbitol in the biological organism to achieve the purpose of insecticidal and innovate the development of pesticide.The study in this paper used the method of virtual screening to find the small molecule inhibitor of SDHDacarbazine(Da-c),which can inhibit the activity of SDH in vitro and the cell level,and obtain the key structure information of combining of SDH and Da-c through the structureactivity relationship.We can use Da-c to synthesis its derivative-((5E)-5-(pyrrolidin-1-ylhydrazinylidene)imidazole-4-carboxamide,Der),which has a stronger ability of inhibitory.In order to detect the non-specific toxicity of Da-c and Der,we use the method of CCK-8 and vivo tests.The results show that Da-c and Der have low toxicity in vivo and in vitro.Through this research,we get a new small molecule inhibitor which has a new structure and a stronger ability of inhibitory which is expected to be a tool as a insecticide which has ability to restrict the growth and development of Lepidoptera,which means that we can stop the development of the lepidoptera during their diapause stage.