Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2020-11-06 , DOI: 10.1016/j.bmc.2020.115837 Emma K Davison 1 , John E McGowan 2 , Freda F Li 2 , Andrew D Harper 2 , Joo Young Jeong 2 , Sonya Mros 3 , Nichaela Harbison-Price 3 , Essie M Van Zuylen 3 , Melanie K Knottenbelt 3 , Adam Heikal 3 , Scott A Ferguson 3 , Michelle A McConnell 3 , Gregory M Cook 4 , Woravimol Krittaphol 5 , Greg F Walker 5 , Margaret A Brimble 1 , David Rennison 2
A series of C-2 derivatized 8-sulfonamidoquinolines were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc (50 µM ZnSO4). The vast majority of compounds tested were demonstrated to be significantly more active against S. uberis when in the presence of supplementary zinc (MICs as low as 0.125 µg/mL were observed in the presence of 50 µM ZnSO4). Compounds 5, 34-36, 39, 58, 79, 82, 94 and 95 were shown to display the greatest antibacterial activity against S. aureus (MIC ≤8 µg/mL; both in the presence and absence of supplementary zinc), while compounds 56, 58 and 66 were demonstrated to also exhibit activity against E. coli (MIC ≤16 µg/mL; under all conditions). Compounds 56, 58 and 66 were subsequently confirmed to be bactericidal against all three mastitis pathogens studied, with MBCs (≥3log10 CFU/mL reduction) of ≤32 µg/mL (in both the presence and absence of 50 µM ZnSO4). To validate the sanitizing activity of compounds 56, 58 and 66, a quantitative suspension disinfection (sanitizer) test was performed. Sanitizing activity (>5log10 CFU/mL reduction in 5 min) was observed against both S. uberis and E. coli at compound concentrations as low as 1 mg/mL (compounds 56, 58 and 66), and against S. aureus at 1 mg/mL (compound 58); thereby validating the potential of compounds 56, 58 and 66 to function as topical sanitizers designed explicitly for use in non-human applications.
中文翻译:
C-2 衍生的 8-磺胺喹啉作为抗菌化合物
在补充锌 (50 µM ZnSO 4 )存在和不存在的情况下,评估了一系列 C-2 衍生的 8-磺胺喹啉对常见乳腺炎病原体乳房链球菌、金黄色葡萄球菌和大肠杆菌的抗菌活性。事实证明,当存在补充锌时,绝大多数测试的化合物对乳房链球菌的活性显着提高(在 50 µM ZnSO 4存在下观察到的 MIC 低至 0.125 µg/mL )。化合物5,34 - 36,39,58,79、82、94和95显示出对金黄色葡萄球菌的最大抗菌活性(MIC ≤ 8 µg/mL;在补充锌存在和不存在的情况下),而化合物56、58和66也显示出活性抗大肠杆菌(MIC ≤16 µg/mL;在所有条件下)。随后证实化合物56、58和66对所研究的所有三种乳腺炎病原体具有杀菌作用,MBC(减少≥3log 10 CFU/mL)≤32 µg/mL(在存在和不存在 50 µM ZnSO 4 的情况下))。为了验证化合物的消毒活性56,58和66,进行定量悬浮消毒(消毒剂)试验。消毒活性(> 5log 10 CFU / mL的减少在5分钟),观察到对两种乳房链球菌和大肠杆菌在化合物浓度低至1毫克/毫升(化合物56,58和66),以及对金黄色葡萄球菌在1mg/mL(化合物58);从而验证化合物56、58和66的潜力 用作明确设计用于非人类应用的局部消毒剂。