National Demonstration Center for Experimental Chemistry Education, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem. 2018 Aug 7;26(14):4145-4152. doi: 10.1016/j.bmc.2018.07.003. Epub 2018 Jul 4.
Two series of ω-phenoxy contained acylhydroxamic acids as novel urease inhibitors were designed and synthesized. Biological activity evaluations revealed that ω-phenoxypropinoylhydroxamic acids were more active than phenoxyacetohydroxamic acids. Out of these compounds, 3-(3,4-dichlorophenoxy)propionylhydroxamic acid c24 showed significant potency against urease in both cell free extract (IC = 0.061 ± 0.003 μM) and intact cell (IC = 0.89 ± 0.05 μM), being over 450- and 120-fold more potent than the clinically prescribed urease inhibitor AHA, repectively. Non-linear fitting of experimental data (V-[S]) suggested a mixed-type inhibition mechanism and a dual site binding mode of these compounds.
设计并合成了两个系列的含ω-苯氧基的酰基羟肟酸作为新型脲酶抑制剂。生物活性评价表明，ω-苯氧基丙酰羟肟酸比苯氧基乙酰羟肟酸更具活性。在这些化合物中，3-(3,4-二氯苯氧基)丙酰羟肟酸 c24 对无细胞提取物（IC=0.061±0.003μM）和完整细胞（IC=0.89±0.05μM）中的脲酶均表现出显著的抑制活性，分别比临床使用的脲酶抑制剂 AHA 高 450 倍和 120 倍。实验数据（V-[S]）的非线性拟合表明，这些化合物具有混合抑制机制和双结合模式。
