Design, synthesis, and biological evaluation of novel analogues of archazolid: a highly potent simplified V-ATPase inhibitor.
Novel analogues of the V-ATPase inhibitors archazolid A and B with modifications of the free hydroxyl groups and the side chain were designed by molecular modeling, synthesized by derivatization of the parent natural product and evaluated for V-ATPase inhibition and growth inhibition of murine connective tissue cells.
Menche
Dirk
D
Helmholtz-Zentrum für Infektionsforschung GmbH, Medizinische Chemie, Inhoffenstrasse 7, 38124 Braunschweig, Germany. dirk.menche@heimholtz-hzi.de
Hassfeld
Jorma
J
Sasse
Florenz
F
Huss
Markus
M
Wieczorek
Helmut
H
D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D018942:Macrolides / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009231:Myxococcales / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
D050256:Antimitotic Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D018942:Macrolides; D013844:Thiazoles; C519727:archazolid A; C519728:archazolid B; D025262:Vacuolar Proton-Translocating ATPases