苯磺酰氨基氧肟酸类脲酶抑制剂的合成及活性研究  

Synthesis and Evaluation of Phenylsulfonylacetohyroxamic Acids as Urease Inhibitors

作　　者：赵明明[1] 刘妹玲 肖竹平[2] ZHAO Ming-ming;LIU Mei-ling;XIAO Zhu-ping(Department of Criminal Science and Technology,Hunan Police Academy,Changsha 410138,China;School of Chemistry and Chemical Engineering,Jishou University,Jishou 416000,China)

机构地区：[1]湖南警察学院刑事科学技术系,湖南长沙410138 [2]吉首大学化学化工学院,湖南吉首416000

出　　处：《化学试剂》2023年第9期154-162,共9页Chemical Reagents

基　　金：国家自然科学基金项目(22267008);湖南省自然科学基金项目(2022JJ80095)。

摘　　要：脲酶抑制剂在医药、农业、畜牧业领域均有重要的应用,以ω-氨基氧肟酸为先导化合物,在氨基上引入磺酰基,合成了7个N-磺酰基取代ω-氨基氧肟酸类新型脲酶抑制剂,其中N-(4-氯苯基)-N-4-叔丁基苯磺酰氨基乙酰氧肟酸活性最高(IC_(50)=(3.78±0.31)μmol/L),是阳性对照乙酰氧肟酸的5倍,对脲酶具有很高的亲和能,K i和K i′分别为(0.233±0.012)和(0.111±0.08)μmol/L。机理研究表明,这是一类脲酶的可逆抑制剂,具有混合型抑制机制。Urease inhibitors have important applications in the fields of medicine,agriculture,and animal husbandry.A series of novel urease inhibitors,N-sulfonyl substitutedω-aminohydroxamic acids,were given by modification of the lead compoundω-aminohydroxamic acid.They showed good potency with N-(4-chlorophenyl)-N-4-tert-butylphenylsulfonylacetohyroxamic acid being the most active(IC_(50)=(3.78±0.31)μmol/L),which showed 5-fold higher potency than that of the positive control acetoximic acid with K i and K i′of(0.233±0.012)and(0.111±0.08)μmol/L,respectively.The mechanism studies revealed that this is a reversible urease inhibitor with a mixed inhibition mechanism.

关 键 词：脲酶抑制剂 ω-氨基氧肟酸 苯磺酰氨基乙酰氧肟酸 乙酰氧肟酸 分子对接 

分 类 号：O62[理学—有机化学]