Department of Chemistry and Biochemistry , University of North Carolina at Greensboro , Greensboro , North Carolina 27402 , United States.
Department of Pharmaceutical Sciences, College of Pharmacy , University of New Mexico , Albuquerque , New Mexico 87131 , United States.
J Nat Prod. 2019 Mar 22;82(3):550-558. doi: 10.1021/acs.jnatprod.8b00925. Epub 2019 Feb 7.
Current treatment options for bacterial infections are dependent on antibiotics that inhibit microbial growth and viability. These approaches result in the evolution of drug-resistant strains of bacteria. An anti-infective strategy that is less likely to lead to the development of resistance is the disruption of quorum sensing mechanisms, which are involved in promoting virulence. The goal of this study was to identify fungal metabolites effective as quorum sensing inhibitors. Three new prenylated diresorcinols (1-3), along with two known compounds, (4 R) -regiolone and decarboxycitrinone, were isolated from a freshwater fungus (Helotiales sp.) from North Carolina. Their structures were assigned on the basis of HRESIMS and NMR experiments. The structure of compound 1 was confirmed via X-ray diffraction analysis, and its absolute configuration was established by TDDFT-ECD and optical rotation calculations. Compounds 1-3 suppressed quorum sensing in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with IC values ranging from 0.3 to 12.5 μM. These compounds represent potential leads in the development of antivirulence therapeutics.
目前针对细菌感染的治疗选择取决于抗生素，这些抗生素能够抑制微生物的生长和存活。这些方法会导致细菌产生耐药菌株。一种不太可能导致耐药性发展的抗感染策略是破坏群体感应机制，因为这些机制参与促进毒力。本研究的目的是鉴定有效的真菌代谢产物作为群体感应抑制剂。从北卡罗来纳州的一种淡水真菌（Helotiales sp.）中分离出三种新的倍半萜二间苯三酚（1-3）以及两种已知化合物（4R）-regiolone 和 decarboxycitrinone。基于高分辨质谱和 NMR 实验确定了它们的结构。通过 X 射线衍射分析确定了化合物 1 的结构，并通过 TDDFT-ECD 和旋光计算确定了其绝对构型。化合物 1-3 抑制了耐甲氧西林金黄色葡萄球菌（MRSA）临床分离株的群体感应，IC 值范围为 0.3 至 12.5 μM。这些化合物代表了开发抗毒力治疗药物的潜在先导化合物。
