采用HPD100大孔树脂、PRP-512A大孔树脂、硅胶、ODS制备色谱柱等方法,从黄皮茎枝中分离得到1个新的咔唑生物碱化合物,通过UV、IR、HR-ESI-MS、1D/2DNMR、ECD等光谱分析方法对其进行结构鉴定,确定其结构,并命名为Claulamine F (1)。通过抗菌实验筛选,未发现其对金葡菌、绿脓杆菌、大肠杆菌具有显著活性。此外,通过MTT法,化合物1未显示其对5种肿瘤细胞株具有明显细胞毒活性。
The problem of drug resistance of Gram-negative bacteria has become increasingly serious and has aroused widespread public concern.The "super bacteria" producing New Delhi metallo-beta-lactamase(NDM-1) are resistant to almost all β-lactam antibiotics.However, clinically existing β-lactamase inhibitors are ineffective against metallo-β-lactamases(MBLs) including NDM-1.Therefore, effective NDM-1 inhibitors are urgently needed.In this study, a high-throughput screening model for NDM-1 inhibitors was optimized and used to screen NDM-1 inhibitors.As a result, IMB-XH1 was screened out as a novel NDM-1 inhibitor from 52 100 compounds of different sources.The combined use of IMB-XH1 can increase the sensitivity of E.coli BL21(DE3)(pET-30 a(+)-NDM-1) to β-lactam antibiotics.Enzymatic kinetic studies indicate that IMB-XH1 is a non-competitive inhibitor of NDM-1 and also has inhibitory activity against other MBLs such as IMP-4, ImiS and L1.As a novel NDM-1 inhibitor, its activity and mechanism of action need to be further explored.
目的从印度洋深海沉积物中分离可培养海洋放线菌,对获得的一株海洋微生物进行抗革兰阴性菌活性物质研究。方法设计11种分离培养基进行海洋放线菌分离,通过16S r RNA基因序列比对分析确定菌株分类;利用多种色谱方法,对菌株IMB16-059产生的活性物质进行分离纯化,通过波谱学和化学方法鉴定其结构。结果根据菌落表型共分离得68株微生物,经16S r RNA分析表明,其中34株属于放线菌门,覆盖5科5属;其余属于厚壁菌门和变形菌门。25株发酵产物显示出抗革兰阴性菌活性。从赤杆菌IMB16-059中分离鉴定了6个化合物,其结构分别确定为L,L-环(脯氨酸-丙氨酸)(1),L,L-环(脯氨酸-酪氨酸(2)),D,L-环(脯氨酸-酪氨酸)(3),邻氨基苯甲酸(4),胸腺嘧啶(5),1H-喹啉-4-酮(6)。化合物1和4显示出抗铜绿假单胞菌活性,在样品浓度为20μg/片时,抑菌圈直径分别为13和20mm。结论印度洋深海沉积物蕴含丰富的微生物类群,其发酵产物显示出较好的抗革兰阴性菌活性,可为新抗生素发现提供重要的菌种资源。
