绿黄霉素：基于一种罕见的四环素类抗生素骨架的拓展研究

Viridicatumtoxins: Expanding on a Rare Tetracycline Antibiotic Scaffold.

作者信息

Shang Zhuo, Salim Angela A, Khalil Zeinab, Quezada Michelle, Bernhardt Paul V, Capon Robert J

机构信息

Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Queensland 4072, Australia.

出版信息

J Org Chem. 2015 Dec 18;80(24):12501-8. doi: 10.1021/acs.joc.5b02367. Epub 2015 Dec 7.

DOI:10.1021/acs.joc.5b02367

PMID:26605854

Abstract

Viridicatumtoxins, which belong to a rare class of fungal tetracycline-like mycotoxins, were subjected to comprehensive spectroscopic and chemical analysis, leading to reassignment/assignment of absolute configurations and characterization of a remarkably acid-stable antibiotic scaffold. Structure activity relationship studies revealed exceptional growth inhibitory activity against vancomycin-resistant Enterococci (IC50 40 nM), >270-fold more potent than the commercial antibiotic oxytetracycline.

摘要

绿黄霉素属于一类罕见的真菌四环类霉菌毒素，对其进行了全面的光谱和化学分析，从而重新确定/确定了其绝对构型，并对一种非常耐酸的抗生素支架进行了表征。构效关系研究表明，其对耐万古霉素肠球菌具有出色的生长抑制活性（IC50为40 nM），比市售抗生素土霉素的效力高270倍以上。