【作者】 王莉； Yu-Ting Lee； 崔长军； James A.Fraser； Luke W Guddat； 王建国；

【Author】 Li Wang;Yu-Ting Lee;Chang-Jun Cui;James A.Fraser;Luke W Guddat;Jian-Guo Wang;State-Key Laboratory and Institute of Elemento-Organic Chemistry,Nankai University;School of Chemistry and Molecular Biosciences,The University of Queensland;

【机构】 南开大学元素有机化学国家重点实验室； 昆士兰大学化学与生命学院；

【摘要】 乙酰乳酸合成酶(AHAS,E.C.2.2.1.6)催化支链氨基酸的生物合成,是超高效绿色除草剂的重要作用靶标~1。近年来研究发现,白色念珠菌的AHAS基因敲除后,该真菌不再具有致病性~2。据此我们表达纯化了白色念珠菌的AHAS催化亚基,测定了8个商品化磺酰脲除草剂对真菌AHAS和白色念珠菌的抑制活性,发现氯嘧磺隆具有理想活性。在此基础上,设计合成了20余个新的磺酰脲化合物,化合物10c表现出极强的抗白色念珠菌活性~3。研究表明,AHAS可以作为抗致病真菌药物的新颖靶标进行研究。更多还原

【Abstract】 Acetohydroxyacid synthase(AHAS,E.C.2.2.1.6) catalyses the biosynthesis pathway of branched-chain amino acids,and it is an important target for the super-active green herbicides~1.Recent study showed that when the AHAS gene for Candica Albicans was knocked out,the fungus was no longer ivirulent~2.Based on this,we had expressed and purified the catalytic subunit of Candica Albicans AHAS and tested the inhibition of 8 commercial sulfonylurea herbicides against fungal AHAS and Candica Albicans itself,from which chlorimuron ethyl was found to display desirable activity.Therefore we designed and synthesized more than twenty novel sulfonylurea compounds,among which compound 10c exhibited potent antifungal activity.These achievements have demonstrated that AHAS could be considered as a novel target for the research of medicinal antifungal agents.更多还原