Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6.
Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6.
复制标题
DOI：
10.1021/acs.jnatprod.6b00948
复制
发表时间：
2017-01-27
影响因子：
5.1
通讯作者：
Thorson JS
中科院分区：
文献类型：
--
作者：
Shaaban KA;Saunders MA;Zhang Y;Tran T;Elshahawi SI;Ponomareva LV;Wang X;Zhang J;Copley GC;Sunkara M;Kharel MK;Morris AJ;Hower JC;Tremblay MS;Prendergast MA;Thorson JS
链霉菌中 6 种新细菌代谢物 [spoxazomicin D (2)、oxachelins B 和 C (4, 5) 以及羧酰胺 6-8] 和 11 种先前报道的细菌代谢物（1、3、9-12a 和 14-18）的分离和结构阐明。据报告 RM-14-6。根据全面的 1D 和 2D NMR 和质谱数据分析，以及与 2、11 和 12a、b 的合成标准品的直接比较，阐明了结构。还首次提供了已知代谢物来诺霉素 (9) 和来诺霉素钠盐 (10) 的完整 2D NMR 归属。比较分析还为之前报道的几种假定的含氮丙啶化合物（例如马杜他汀 A1、B1、C1（也称为 MBJ-0034）和 MBJ-0035）作为苯酚-二氢恶唑的结构修正提供了基础。生物活性分析[包括抗菌、抗真菌、癌细胞系细胞毒性、未折叠蛋白反应 (UPR) 调节和乙醇损伤神经保护]显示 2 和 5 是有效的神经保护剂，来诺霉素 (9) 及其钠盐 (10) 是有效的 UPR 调节剂，突出了苯酚恶唑啉/水杨酸盐和聚醚药效团的新功能。
The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6–8] and 11 previously reported bacterial metabolites (1, 3, 9–12a, and 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.