University of the Incarnate Word Feik School of Pharmacy, San Antonio, TX, USA.
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Arch Pharm (Weinheim). 2017 Jun;350(6). doi: 10.1002/ardp.201700029. Epub 2017 Apr 21.
In an effort to develop new fluoroquinolones, we synthesized eight compounds and tested them against a panel of bacteria. The design of these compounds was guided by the introduction of the isothiazoloquinolone motif. The three most active compounds in this series, 8-10, demonstrated good antibacterial activity against methicillin-sensitive Staphylococcus aureus and healthcare-acquired methicillin-resistant Staphylococcus aureus (MIC 0.62-6.3 µg/mL). Further, when these three active compounds were tested for their inhibitory effects on bacterial enzymes, compound 9 was the most effective agent exhibiting IC values of 33.9 and 116.5 μM in the S. aureus deoxyribonucleic acid (DNA) gyrase supercoiling and topoisomerase IV decatenation assays, respectively.
为了开发新型氟喹诺酮类药物，我们合成了 8 种化合物，并对其进行了一系列细菌的测试。这些化合物的设计受到异噻唑并喹诺酮基序的引入的指导。在该系列中，三个最活跃的化合物 8-10 对甲氧西林敏感的金黄色葡萄球菌和医疗机构获得性耐甲氧西林金黄色葡萄球菌（MIC 0.62-6.3μg/ml）表现出良好的抗菌活性。此外，当这三种活性化合物被测试其对细菌酶的抑制作用时，化合物 9 是最有效的试剂，在金黄色葡萄球菌脱氧核糖核酸（DNA）拓扑异构酶超螺旋和拓扑异构酶 IV 解链酶试验中，IC 值分别为 33.9 和 116.5μM。
