分会

第五十七分会：农业化学

摘要

天然黄嘌呤类生物碱如茶碱、咖啡碱等与人们的日常饮食密切相关，在农药化学领域已逐渐显示出多样的生物活性，通过黄嘌呤基本骨架引入各种农药活性基团的策略设计合成新型农药先导化合物具有较大的研究潜力和一定应用前景[1-3]。哌嗪衍生物不仅具有医药以及杀虫、抑菌、除草活性，还可作为酮醇还原酸异构酶（KARI）的抑制剂[4-7]。KARI在支链氨基酸的合成中发挥着重要作用，且由于KARI仅存在于微生物和植物体内，以KARI为靶标设计的农药分子具备对人和哺乳动物安全等优点。基于向甲基黄嘌呤中引入哌嗪活性基团的策略，以茶碱、8-氯茶碱和取代哌嗪等为原料，通过亲核取代反应、Mannich反应合成了不同系列的新型7-或8-位含哌嗪基团的黄嘌呤衍生物。生物活性测试结果表明，部分目标化合物对小菜蛾和东方粘虫均表现出一定的杀虫活性，尤其针对小菜蛾，部分化合物在10 mg·L-1浓度下仍具有明显的致死活性；部分化合物对苹果轮纹病菌、油菜菌核病菌和小麦纹枯病菌具有70%以上的抑制率。部分化合物对KARI也展现出良好的抑制活性，值得作为新型KARI抑制剂进行进一步研究。通过分子前线轨道理论计算和高活性化合物与KARI酶结构的分子对接，阐释了化合物的活性基团以及可能的作用方式。本研究结果对基于天然产物结构的新型农药分子设计和开发具有一定的参考意义。 Natural xanthine alkaloids such as theophylline and caffeine are closely related to people's daily diet, and have gradually shown a variety of biological activities in the field of pesticide chemistry. The design and synthesis of novel pesticide lead compounds via the strategy of introducing various pesticidal active groups into the xanthine structural skeleton has great research potential and certain application prospects. Piperazine derivatives not only have pharmaceutical, insecticidal, fungicidal and herbicidal activities, but also are inhibitors of ketol-acid reductoisomerase (KARI) which is a key enzyme catalyzing the synthesis of branched-chain amino acids. As KARI only exists in microorganisms and plants, the designed pesticidal agents targeting KARI should possess the advantages such as safe for human and other mammals. Based on the strategy of introducing bioactive piperazine motif into the methylxanthine skeleton, various series of novel xanthine derivatives with piperazine group at 7-/8- position were synthesized via nucleophilic substitution reaction and Mannich reaction from starting materials of theophylline, 8-chlorotheophylline and substituted piperazines. The bioassay results showed that most of the target compounds exhibited certain insecticidal activities against Mythimna separata Walker and Plutella xylostella L.; especially towards the latter one, partial compounds still exhibited apparent larvicidal activities at a concentration of 10 mg·L-1. Some of the compounds showed > 70% inhibition rate against Physalospora piricola, Sclerotinia sclerotiorum and Rhizoctonia cerealis. Partial compounds also exhibited good inhibitory activities against KARI, and could serve as new KARI inhibitors for further investigation. Through molecular frontier orbital theoretical calculations and molecular docking of highly active compound with KARI enzyme structure, the active groups of the compound and possible mode of action were further elucidated. The results of this study are of reference value for the design and development of novel pesticidal agents based on the structure of natural products.

关键词

黄嘌呤;哌嗪;杀虫活性;杀菌活性;KARI酶

线上墙报仅限年会已缴费参会代表观看。

您还没有登录，请您先 点击这里登录