Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, 8010 Graz, Austria.
Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London WC1E 7HX, UK.
Molecules. 2020 Feb 7;25(3):734. doi: 10.3390/molecules25030734.
Therapeutic treatment options for opportunistic non-tuberculous mycobacterial (NTM) infection and/or serious mycobacterial infections such as tuberculosis (TB) and leprosy are limited due to the spread of antimicrobial resistance mechanism. Plant-derived natural compounds as prospective efflux pump inhibitors may present a promising adjunct to conventional chemotherapy by enhancing mycobacterial susceptibility to antibiotics. This study served to evaluate the antimicrobial and resistance-modifying profile of a range of plant-derived flavonoids against the mycobacterial model strains: , , and BCG. The minimum inhibitory concentrations (MICs) of the compounds against the mycobacterial strains were determined using both agar dilution and broth dilution assays, while their efflux inhibitory activity was investigated via an ethidium bromide-based fluorometric assay. All compounds were screened for their synergistic effects with ethidium bromide (EtBr) and rifampicin (RIF) against . Skullcapflavone II (5,2'-dihydroxy-6,7,8,6'-tetramethoxyflavone, ) exerted potent antimicrobial activity against and BCG and considerably increased the susceptibility of to EtBr and RIF. Nobiletin (5,6,7,8,3',4'-hexamethoxyflavone, ) was determined to be the most potent efflux-inhibitor in and . However, a connection between strong modulatory and putative efflux activity of the compounds could not be observed. Nevertheless, the results highlight two polymethoxyflavones, skullcapflavone II and nobiletin, with potent antimycobacterial and antibiotic resistance modulating activities as valuable adjuvants in anti-mycobacterial therapies.
由于抗菌药物耐药机制的传播，机会性非结核分枝杆菌（NTM）感染和/或严重分枝杆菌感染（如肺结核[TB]和麻风病）的治疗选择有限。植物来源的天然化合物作为潜在的外排泵抑制剂，通过增强分枝杆菌对抗生素的敏感性，可能为传统化疗提供一种很有前途的辅助手段。本研究旨在评估一系列植物来源的类黄酮对分枝杆菌模型菌株的抗菌和耐药修饰特性： 、 、 和 BCG。使用琼脂稀释和肉汤稀释测定法测定化合物对分枝杆菌菌株的最小抑菌浓度（MICs），同时通过基于溴化乙锭的荧光测定法研究其外排泵抑制活性。所有化合物均针对其与溴化乙锭（EtBr）和利福平（RIF）对 的协同作用进行了筛选。黄芩素 II（5,2'-二羟基-6,7,8,6'-四甲氧基黄酮， ）对 和 BCG 表现出强大的抗菌活性，并显著增加了 对 EtBr 和 RIF 的敏感性。诺必灵（5,6,7,8,3',4'-六甲氧基黄酮， ）被确定为 和 中最强的外排抑制剂。然而，并没有观察到化合物的强调节和假定的外排活性之间存在联系。尽管如此，这些结果突出了两种具有多甲氧基黄酮结构的化合物，黄芩素 II 和诺必灵，具有强大的抗分枝杆菌和抗生素耐药修饰活性，可作为抗分枝杆菌治疗的有价值的佐剂。
