title: Archazolid A-15-O-β-D-glucopyranoside and iso-archazolid B: potent V-ATPase inhibitory polyketides from the myxobacteria Cystobacter violaceus and Archangium gephyra.
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.
authors.affiliation: Institut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Horstmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Essig
authors.forename: Svenja
authors.initials: S
authors.lastname: Bockelmann
authors.forename: Helmut
authors.initials: H
authors.lastname: Wieczorek
authors.forename: Markus
authors.initials: M
authors.lastname: Huss
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.forename: Dirk
authors.initials: D
authors.lastname: Menche
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009231:Myxococcales / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D005960:Glucosides; D018942:Macrolides; D013844:Thiazoles; C519727:archazolid A; C560157:archazolid A-15-O-beta-D-glucopyranoside; C519728:archazolid B; D025262:Vacuolar Proton-Translocating ATPases