Kotb Ahmed, Abutaleb Nader S, Hagras Mohamed, Bayoumi Ashraf, Moustafa Mahmoud M, Ghiaty Adel, Seleem Mohamed N, Mayhoub Abdelrahman S
Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University Cairo 11884 Egypt
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University West Lafayette IN USA 47907
RSC Adv. 2019 Feb 26;9(12):6770-6778. doi: 10.1039/c8ra10525a. eCollection 2019 Feb 22.
The structure-activity and structure-kinetic relationships of a new -butylphenylthiazole series with oxadiazole linkers were conducted with the objective of obtaining a new orally available antibacterial compounds. Twenty-two new compounds were prepared, purified and identified. Their activity against methicillin-resistant were examined. Compound 20 with 3-hydroxyazetidine as a nitrogenous side chain showed promising activity against twenty-four clinical isolates, including vancomycin-resistant staphylococcal and enterococcal species with MIC values ranging from 4-8 μg mL. Additional advantages of this compound include an ability to eradicate staphylococcal biofilm mass in a dose-dependent manner as well as high metabolic stability after an oral dose of 25 mg kg with a biological half-life that exceeds 5 hours and a plasma concentration ( ) that exceeds the MIC values.
为了获得新型口服可用抗菌化合物，对带有恶二唑连接基的新型丁基苯基噻唑系列进行了构效关系和构动关系研究。制备、纯化并鉴定了22种新化合物。检测了它们对耐甲氧西林菌的活性。以3-羟基氮杂环丁烷为含氮侧链的化合物20对24株临床分离菌显示出有前景的活性，包括耐万古霉素葡萄球菌和肠球菌属，其最低抑菌浓度（MIC）值为4 - 8μg/mL。该化合物的其他优点包括能够以剂量依赖方式消除葡萄球菌生物膜，口服25mg/kg后具有高代谢稳定性，生物半衰期超过5小时，血浆浓度超过MIC值。
