Al-Tannak Naser F, Phillips Oludotun A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Sci Pharm. 2017 Oct 2;85(4):34. doi: 10.3390/scipharm85040034.
Twelve -substituted-glycinyl triazolyl oxazolidinone derivatives were screened for antimycobacterial activity against susceptible ( ( H37Rv) and resistant (isoniazid (INH)-resistant (SRI 1369), rifampin (RMP)-resistant (SRI 1367), and ofloxacin (OFX)-resistant (SRI 4000)) strains. Most of the compounds showed moderate to strong antimycobacterial activity against all strains tested, with minimum inhibitory concentration (MIC) value ranges of 0.5-11.5, 0.056-11.6, 0.11-5.8, and 0.03-11.6 μM, and percent inhibition ranges of 41-79%, 51-72%, 50-75%, and 52-71% against H37Rv, INH-R, RMP-R, and OFX-R , respectively. The 3,5-dinitrobenzoyl and 5-nitrofuroyl derivatives demonstrated strong antimycobacterial activities with the -(5-nitrofuroyl) derivatives ( and ) being the most potent, with MIC value range of 0.3-0.6 μM against all strains tested. Compounds were not bactericidal, but showed intracellular (macrophage) antimycobacterial activity. A reliable validated analytical method was developed for a representative compound using Waters Acquity ultra High-Performance Liquid Chromatography (UHPLC) system with quaternary Solvent Manager (H-Class). A simple extraction method indicated that was stable in human plasma after 90 min at 37 °C with more than 90% successfully recovered. Moreover, stress stability studies were performed and degradants were identified by using UHPLC-ESI-QToF under acidic, basic, and oxidative simulated conditions.
对12-取代甘氨酰三唑基恶唑烷酮衍生物进行了筛选，以检测其对敏感菌株（H37Rv）和耐药菌株（耐异烟肼（INH）的SRI 1369、耐利福平（RMP）的SRI 1367和耐氧氟沙星（OFX）的SRI 4000）的抗分枝杆菌活性。大多数化合物对所有测试菌株均表现出中度至强的抗分枝杆菌活性，其最低抑菌浓度（MIC）值范围为0.5 - 11.5、0.056 - 11.6、0.11 - 5.8和0.03 - 11.6 μM，对H37Rv、INH-R、RMP-R和OFX-R的抑制率范围分别为41 - 79%、51 - 72%、50 - 75%和52 - 71%。3,5-二硝基苯甲酰基和5-硝基呋喃甲酰基衍生物表现出较强的抗分枝杆菌活性，其中-(5-硝基呋喃甲酰基)衍生物（和）最为有效，对所有测试菌株的MIC值范围为0.3 - 0.6 μM。这些化合物无杀菌作用，但具有细胞内（巨噬细胞）抗分枝杆菌活性。使用配备四元溶剂管理器（H-Class）的沃特世Acquity超高效液相色谱（UHPLC）系统，为一种代表性化合物开发了一种可靠的经过验证的分析方法。一种简单的提取方法表明，在37°C下90分钟后，该化合物在人血浆中稳定，回收率超过90%。此外，还进行了应力稳定性研究，并在酸性、碱性和氧化模拟条件下使用UHPLC-ESI-QToF鉴定了降解产物。
