Pervez Humayun, Iqbal Mohammad S, Tahir Muhammad Younas, Nasim Faiz-ul-Hassan, Choudhary Muhammad Iqbal, Khan Khalid Mohammed
Department of Chemistry, Bahauddin Zakariya University, Multan, Pakistan.
J Enzyme Inhib Med Chem. 2008 Dec;23(6):848-54. doi: 10.1080/14756360701746179.
A series of 15 previously reported N(4)-substituted isatin-3-thiosemicarbazones 3a-o has been screened for cytotoxic, antibacterial, antifungal and urease inhibitory activities. Compounds 3b, 3e and 3n proved to be active in cytotoxicity assay; 3e exhibited a high degree of cytotoxic activity (LD(50) = 1.10 x 10(-5) M). Compound 3h exhibited significant antibacterial activity against B. subtilis, whereas compounds 3a, 3k and 3l displayed significant antifungal activity against one or more fungal strains i.e. T. longifusus, A. flavus and M. canis. In human urease enzyme inhibition assay, compounds 3g, 3k and 3m proved to be the most potent inhibitors, exhibiting relatively pronounced inhibition of the enzyme. These compounds, being non-toxic, could be potential candidates for orally effective therapeutic agents to treat certain clinical conditions induced by bacterial ureases like H. pylori urease. This study presents the first example of inhibition of urease by isatin-thiosemicarbazones and as such provides a solid basis for further research on such compounds to develop more potent inhibitors.
对一系列先前报道的15种N(4)-取代异吲哚-3-硫代半卡巴腙3a-o进行了细胞毒性、抗菌、抗真菌和脲酶抑制活性筛选。化合物3b、3e和3n在细胞毒性试验中被证明具有活性；3e表现出高度的细胞毒性活性（半数致死剂量LD(50)=1.10×10⁻⁵ M）。化合物3h对枯草芽孢杆菌表现出显著的抗菌活性，而化合物3a、3k和3l对一种或多种真菌菌株即长柄木霉、黄曲霉和犬小孢子菌表现出显著的抗真菌活性。在人脲酶抑制试验中，化合物3g、3k和3m被证明是最有效的抑制剂，对该酶表现出相对明显的抑制作用。这些化合物无毒，可能是治疗由细菌脲酶如幽门螺杆菌脲酶引起的某些临床病症的口服有效治疗剂的潜在候选物。本研究首次展示了异吲哚-硫代半卡巴腙对脲酶的抑制作用，因此为进一步研究此类化合物以开发更有效的抑制剂提供了坚实的基础。
