八胺霉素A和B，对恶性疟原虫有活性的环状八肽缩酚酸肽

Octaminomycins A and B, Cyclic Octadepsipeptides Active against Plasmodium falciparum.

作者信息

Jang Jun-Pil, Nogawa Toshihiko, Futamura Yushi, Shimizu Takeshi, Hashizume Daisuke, Takahashi Shunji, Jang Jae-Hyuk, Ahn Jong Seog, Osada Hiroyuki

机构信息

RIKEN Global Research Cluster , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology , Cheongju, 28116, South Korea.

出版信息

J Nat Prod. 2017 Jan 27;80(1):134-140. doi: 10.1021/acs.jnatprod.6b00758. Epub 2017 Jan 5.

DOI:10.1021/acs.jnatprod.6b00758

PMID:28055207

Abstract

Two new cyclic octadepsipeptides, octaminomycins A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces sp. RK85-270 based on Natural Products Plot screening. Their structures were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopic data, and MS/MS experiments for sequence analysis. The absolute configurations of the constituent amino acid residues were determined by a combination of single-crystal X-ray diffraction and Marfey's methodology. Notably, octaminomycins A (1) and B (2) showed good in vitro antiplasmodial activity against chloroquine-sensitive as well as chloroquine-resistant strains with no cytotoxicity up to 30 μM.

摘要

基于天然产物图谱筛选，从链霉菌属RK85 - 270的微生物代谢物组分库中分离出两种新的环状八肽缩酚酸肽，八胺霉素A（1）和B（2）。基于高分辨电喷雾电离质谱（HRESIMS）、一维和二维核磁共振光谱数据以及用于序列分析的串联质谱实验，阐明了它们的结构。通过单晶X射线衍射和马尔菲方法相结合，确定了组成氨基酸残基的绝对构型。值得注意的是，八胺霉素A（1）和B（2）对氯喹敏感及氯喹耐药菌株均表现出良好的体外抗疟活性，在高达30 μM的浓度下无细胞毒性。