1. Archazolid A-15-O-β-<scp>d</scp>-glucopyranoside and iso-Archazolid B: Potent V-ATPase Inhibitory Polyketides from the Myxobacteria Cystobacter violaceus and Archangium gephyra
- Author
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Helmut Wieczorek, Florenz Sasse, Markus Huss, Sebastian Essig, Svenja Bockelmann, Dirk Menche, Nicole Horstmann, and Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
- Subjects
Male ,Vacuolar Proton-Translocating ATPases ,The Myxobacteria ,Stereochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Inhibitory postsynaptic potential ,Analytical Chemistry ,Inhibitory Concentration 50 ,Mice ,chemistry.chemical_compound ,Glucosides ,Drug Discovery ,Structural isomer ,Animals ,Humans ,V-ATPase ,Myxococcales ,Archazolid B ,Pharmacology ,chemistry.chemical_classification ,Natural product ,Molecular Structure ,Organic Chemistry ,Glycoside ,Cystobacter violaceus ,Thiazoles ,Complementary and alternative medicine ,chemistry ,Molecular Medicine ,Female ,Macrolides ,Drug Screening Assays, Antitumor - Abstract
Two structurally novel analogues of the macrolides archazolids A and B, archazolid A-15-O-β-D-glucopyranoside (archazolid E, 5) and iso-archazolid B (archazolid F, 6), were isolated from the myxobacterium Cystobacter violaceus and Archangium gephyra, respectively. Macrolactone 5 represents the first 15-O-glycoside of the archazolids. iso-Archazolid B (6) incorporates a C-3 alkene and presents the first constitutional isomer reported for this natural product class. The structures of these polyketides were determined by spectroscopic analysis, in particular by HMBC, HMQC, and ROESY NMR investigations and by chemical degradation. iso-Archazolid B (6) demonstrated extremely high antiproliferative and V-ATPase inhibitory effects, with IC(50) values in the picomolar range, while only moderate activity was observed for glycoside 5. iso-Archazolid B presents the most potent archazolid known.
- Published
- 2011
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