Akhtar Tashfeen, Khan Muhammad A, Iqbal Jamshed, Jones Peter G, Hameed Shahid
Department of Chemistry, Mirpur University of Science and Technology (MUST), Mirpur, Azad Jammu and Kashmir, 10250, Pakistan; Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
Chem Biol Drug Des. 2014 Jul;84(1):92-8. doi: 10.1111/cbdd.12297. Epub 2014 Jun 5.
A one-pot method for the synthesis of structural type urease inhibitors, 2-amino-1,3,4-oxadiazoles, was developed. The structures of the compounds were established using spectroanalytical techniques and unambiguously confirmed by single-crystal X-ray analysis of compound 3o. The synthesized compounds were tested against jack beans urease, and most of the compounds (3c, 3g, 3j, 3k, 3n, 3r-3v) were found more active than the standard. The most potent compound (3u) had an IC50 value of 6.03 ± 0.02 μm as compared to the IC50 value of the standard (thiourea; 22.0 ± 1.2 μm). The prominent urease inhibition activity of these compounds may serve as an important finding in the development of less toxic and more potent antiulcer drugs. The compounds were also investigated against four bacterial strains, and some of the compounds (3g and 3r) were found more potent than the standard drug (ciprofloxacin) against all the tested strains. The MIC value for compound 3g was 0.156 μmol/mL against the tested bacterial strains.
开发了一种用于合成结构类型脲酶抑制剂2-氨基-1,3,4-恶二唑的一锅法。使用光谱分析技术确定了化合物的结构，并通过化合物3o的单晶X射线分析明确证实。对合成的化合物进行了刀豆脲酶测试，发现大多数化合物（3c、3g、3j、3k、3n、3r - 3v）比标准品更具活性。最有效的化合物（3u）的IC50值为6.03±0.02μm，而标准品（硫脲；22.0±1.2μm）的IC50值为22.0±1.2μm。这些化合物突出的脲酶抑制活性可能是开发低毒高效抗溃疡药物的一项重要发现。还对这些化合物针对四种细菌菌株进行了研究，发现一些化合物（3g和3r）对所有测试菌株的活性比标准药物（环丙沙星）更强。化合物3g对测试细菌菌株的MIC值为0.156μmol/mL。
