• Archazolid A-15-O-β-D-glucopyranoside and iso-archazolid B: potent V-ATPase inhibitory polyketides from the myxobacteria Cystobacter violaceus and Archangium gephyra.

      Horstmann, Nicole; Essig, Sebastian; Bockelmann, Svenja; Wieczorek, Helmut; Huss, Markus; Sasse, Florenz; Menche, Dirk; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2011-05-27)
      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.
    • Archazolid and apicularen: novel specific V-ATPase inhibitors.

      Huss, Markus; Sasse, Florenz; Kunze, Brigitte; Jansen, Rolf; Steinmetz, Heinrich; Ingenhorst, Gudrun; Zeeck, Axel; Wieczorek, Helmut; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2005-08-04)
      V-ATPases constitute a ubiquitous family of heteromultimeric, proton translocating proteins. According to their localization in a multitude of eukaryotic membranes, they energize many different transport processes. Since their malfunction is correlated with various diseases in humans, the elucidation of the properties of this enzyme for the development of selective inhibitors and drugs is one of the challenges in V-ATPase research.