Son Sangkeun, Ko Sung-Kyun, Jang Mina, Lee Jae Kyoung, Kwon Min Cheol, Kang Dong Hyo, Ryoo In-Ja, Lee Jung-Sook, Hong Young-Soo, Kim Bo Yeon, Jang Jae-Hyuk, Ahn Jong Seog
Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology , Cheongju 28116, Korea.
Department of Biomolecular Science, University of Science and Technology , Daejeon 34141, Korea.
J Nat Prod. 2017 May 26;80(5):1378-1386. doi: 10.1021/acs.jnatprod.6b01059. Epub 2017 Apr 13.
A bioassay-guided investigation in conjunction with chemical screening led to the isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy-α-l-talopyranoside (2), and naphthomycinoside (3), along with three known secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures were elucidated by detailed NMR and MS spectroscopic analyses. Absolute configurational analysis of the sugar units based on the magnitudes of the coupling constants, NOESY correlations, chemical derivatization, and optical rotation measurements revealed that compounds 1-3 and 5 incorporate the rare deoxyhexose 6-deoxy-α-l-talopyranose. The absolute configuration of a polyketide extender unit of 3 was determined by applying the J-based configuration analysis and modified Mosher's method. Ulleungoside (1) and naphthomycin A (7) showed in vitro inhibitory effects against indoleamine 2,3-dioxygenase activity. Further bioevaluation revealed that compounds 1 and 7 had moderate antiproliferative activities against several cancer cell lines, and compounds 5 and 6, which are members of the piericidin family, induced autophagosome accumulation.
通过生物活性测定指导的研究并结合化学筛选，从链霉菌属菌株KCB13F030中分离出三种新的糖苷，郁陵岛苷（1）、2-甲基氨基苯甲酰基6-脱氧-α-L-塔罗吡喃糖苷（2）和萘霉素糖苷（3），以及三种已知的次生代谢产物（5-7）。通过详细的核磁共振（NMR）和质谱（MS）光谱分析阐明了它们的结构。基于耦合常数的大小、核Overhauser效应光谱（NOESY）相关性、化学衍生化和旋光测量对糖单元进行的绝对构型分析表明，化合物1-3和5含有罕见的脱氧己糖6-脱氧-α-L-塔罗吡喃糖。通过应用基于J的构型分析和改进的莫舍尔方法确定了3的聚酮链延伸单元的绝对构型。郁陵岛苷（1）和萘霉素A（7）对吲哚胺2,3-双加氧酶活性表现出体外抑制作用。进一步的生物评价表明，化合物1和7对几种癌细胞系具有中等的抗增殖活性，而作为哌啶菌素家族成员的化合物5和6诱导自噬体积累。
