Koyama Nobuhiro, Sato Hirofumi, Tomoda Hiroshi
Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan.
Acta Pharm Sin B. 2015 Nov;5(6):564-8. doi: 10.1016/j.apsb.2015.07.010. Epub 2015 Nov 2.
In an analytical study of microbial broths, the actinomycete strain Kitasatospora sp. P07101 was found to produce three new congeners, which were designated hazimycins B (1), C (2), and D (3), together with the previously reported hazimycin (renamed hazimycin A (4)). The structures of these hazimycins were examined using various spectroscopic methods including nuclear magnetic resonance (NMR), and the results revealed that 1-3 were analogues of hazimycin with the replacement of one of the two isonitrile groups in 4 by an NH-formyl group in 1, the two isonitrile groups and an amide group by two NH-formyl groups and a nitrile group in 2, and the two isonitrile groups and two amide groups by two NH-formyl groups and two nitrile groups in 3. Only hazimycin A exhibited moderate antimicrobial activities against Gram-positive bacteria and Candida albicans. These results indicated that the presence of two isonitrile groups in the hazimycin structure is essential for antimicrobial activity.
在一项对微生物发酵液的分析研究中,发现放线菌菌株北里孢菌属(Kitasatospora sp.)P07101产生了三种新的同系物,分别命名为哈齐霉素B(1)、C(2)和D(3),同时还产生了先前报道的哈齐霉素(重新命名为哈齐霉素A(4))。使用包括核磁共振(NMR)在内的各种光谱方法对这些哈齐霉素的结构进行了研究,结果表明,1-3是哈齐霉素的类似物,其中1中4的两个异腈基团之一被NH-甲酰基取代,2中4的两个异腈基团和一个酰胺基团被两个NH-甲酰基和一个腈基团取代,3中4的两个异腈基团和两个酰胺基团被两个NH-甲酰基和两个腈基团取代。只有哈齐霉素A对革兰氏阳性菌和白色念珠菌表现出中等抗菌活性。这些结果表明,哈齐霉素结构中两个异腈基团的存在对抗菌活性至关重要。