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抗菌合成类黄酮BrCl-黄酮通过破坏细胞膜完整性展现出重要的抗活性。

The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti- Activity by Damaging Cell Membrane Integrity.

作者信息

Babii Cornelia, Savu Mihaela, Motrescu Iuliana, Birsa Lucian Mihail, Sarbu Laura Gabriela, Stefan Marius

机构信息

Biology Department, Faculty of Biology, The Alexandru Ioan Cuza University of Iasi, Bld. Carol I, Nr. 11, 700506 Iasi, Romania.

Sciences Department, Research Institute for Agriculture and Environment, Iasi University of Life Sciences, 3 Sadoveanu Alley, 700490 Iasi, Romania.

出版信息

Pharmaceuticals (Basel). 2021 Nov 6;14(11):1130. doi: 10.3390/ph14111130.

Abstract

Infections caused by are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against , , and . The investigation of anti- mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of spp. multidrug resistance phenomenon.

摘要

由……引起的感染由于抗真菌耐药性增加而极难治疗。最近的研究表明,对氟康唑耐药的……感染患者的治疗选择非常有限。因此,寻找新的高效抗真菌药物是医学上的当务之急。本研究的目的是探索BrCl-黄酮(一种新型合成黄酮类化合物,在苯并吡喃核心以溴作为卤素取代基)对四种……临床菌株的抗真菌潜力。最低抑菌浓度和最低杀菌浓度的测定以及时间杀菌试验表明,BrCl-黄酮对……、……、……和……具有很强的抗真菌作用。使用荧光显微镜和扫描电子显微镜对抗真菌作用机制的研究表明,Br-Cl黄酮可通过损害膜完整性来抑制真菌生长,由此产生的结构损伤导致细胞裂解。BrCl-黄酮对……菌还表现出重要的抗毒力特性,抑制生物膜形成和酵母向菌丝的转变。当BrCl-黄酮与氟康唑联合使用时,观察到对……菌株有很强的协同抗真菌作用。在……菌多重耐药现象的背景下,BrCl-黄酮具有开发新型有效抗真菌药物的良好潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59f8/8622092/ce1ff2f28c0f/pharmaceuticals-14-01130-g001.jpg

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