尿素酶
恶二唑
化学
间苯二甲酸
硫脲
组合化学
甲醇
联氨(抗抑郁剂)
水合物
有机化学
酶
生物化学
聚酯纤维
对苯二甲酸
作者
Sana Shah,Momin Khan,Mahboob Ali,Abdul Wadood,Ashfaq Ur Rehman,Zarbad Shah,Muhammad Yousaf,Uzma Salar,Khalid Mohammed Khan
出处
期刊:Medicinal Chemistry
日期:2022-08-01
卷期号:18 (7): 820-830
被引量:10
标识
DOI:10.2174/1573406418666220301161934
摘要
Synthesis of bis-1,3,4-oxadiazole derivatives as novel and potential urease inhibitors.Despite many important biological activities associated with oxadiazoles, they are still neglected by medicinal chemists for their possible urease inhibitory activity. Keeping in view the countless importance of urease inhibitors, we have synthesized a new library of substituted bis-oxadiazole derivatives (1-21) to evaluate their urease inhibitory potential.Synthesis of substituted bis-oxadiazole derivatives (1-21) to evaluate their urease inhibitory potential.Bis-1,3,4-oxadiazole derivatives 1-21 were synthesized through sequential reactions using starting material isophthalic acid. Esterification reaction was done by refluxing in methanol for 2 h in the presence of the catalytic amount of concentrated H2SO4 till dissolution. In the second step, dimethyl isophthalate and hydrazine hydrate in excess (1:5) were refluxed in methanol to afford isophthalic dihydrazide. Then, isophthalic dihydrazide was treated with different substituted benzaldehydes in a 1:2 ratio under acidic conditions Result: In vitro urease, the inhibitory activity of the synthesized compounds were evaluated and results demonstrated good activities with IC50 values in the range of 13.46 ± 0.34 to 74.45 ± 3.81 µM as compared to the standard thiourea (IC50 = 21.13 ± 0.415 µM). Most of the compounds were found to be more potent than the standard. The structure-activity relationship (SAR) suggested that the variations in the inhibitory activities of the compounds were due to different substitutions. Furthermore; in silico study was also performed.Current study identified a new class of urease inhibitors. All synthetic compounds 1-21 showed potent as well as good to moderate urease inhibitory activities except 3. SAR suggested that hydroxy-bearing analogs were identified exceptionally good. Molecular docking revealed many important interactions made by compounds with the active site of the urease enzyme.
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