Viridicatumtoxins: Expanding on a Rare Tetracycline Antibiotic Scaffold

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

doi:10.1021/acs.joc.5b02367

Viridicatumtoxins: Expanding on a Rare Tetracycline Antibiotic Scaffold

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

Authors

Zhuo Shang¹, Angela A Salim¹, Zeinab Khalil¹, Michelle Quezada¹, Paul V Bernhardt¹, Robert J Capon¹

Affiliation

¹ Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Queensland 4072, Australia.

PMID: 26605854
DOI: 10.1021/acs.joc.5b02367

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Enterococcus / drug effects*
Metallothionein 3
Microbial Sensitivity Tests
Mycotoxins / analysis*
Mycotoxins / chemistry*
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / pharmacology*
Oxytetracycline / chemistry*
Oxytetracycline / pharmacology*
Structure-Activity Relationship
Tetracycline Resistance / drug effects*
Tetracyclines / chemistry*
Tetracyclines / pharmacology*
Vancomycin Resistance / drug effects*

Substances

Anti-Bacterial Agents
Metallothionein 3
Mycotoxins
Nerve Tissue Proteins
Tetracyclines
viridicatumtoxin
Oxytetracycline