Khan Khalid Mohammed, Rahim Fazal, Khan Ajmal, Shabeer Muhammad, Hussain Shafqat, Rehman Wajid, Taha Muhammad, Khan Momin, Perveen Shahnaz, Choudhary M Iqbal
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Department of Chemistry, Hazara University, Mansehra, Pakistan.
Bioorg Med Chem. 2014 Aug 1;22(15):4119-23. doi: 10.1016/j.bmc.2014.05.057. Epub 2014 Jun 2.
A series of thiobarbituric acid derivatives 1-27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1-27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1 ± 0.52, 16.0 ± 0.45, 16.0 ± 0.22, 14.3 ± 0.27, 6.7 ± 0.27, 10.6 ± 0.17, 19.2 ± 0.29, 18.2 ± 0.76 and 1.61 ± 0.18 μM, respectively, much better than the standard urease inhibitor thiourea (IC₅₀=21 ± 0.11 μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC₅₀ values 21.4 ± 1.04 and 21.5 ± 0.61 μM, 22.8 ± 0.32, 25.2 ± 0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure-activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and (1)H NMR.
合成了一系列硫代巴比妥酸衍生物1 - 27，并对其脲酶抑制潜力进行了评估。对这些化合物1 - 27的筛选获得了令人兴奋的结果。化合物5、7、8、11、16、17、22、23和24表现出优异的脲酶抑制活性，IC50值分别为18.1±0.52、16.0±0.45、16.0±0.22、14.3±0.27、6.7±0.27、10.6±0.17、19.2±0.29、18.2±0.76和1.61±0.18μM，远优于标准脲酶抑制剂硫脲（IC₅₀ = 21±0.11μM）。化合物3、4、10和26表现出与标准相当的活性，IC50值分别为21.4±1.04和21.5±0.61μM、22.8±0.32、25.2±0.63。然而，其余化合物也显示出显著的抑制潜力。建立了这些化合物的构效关系。本研究鉴定出了一类新型脲酶抑制剂。所有化合物的结构均通过EI-MS和¹H NMR等光谱技术得以确证。
