A novel acyclic oligomycin A derivative formed via retro-aldol rearrangement of oligomycin A.

Abstract

The antibiotic oligomycin A in the presence of K(2)CO(3) and n-Bu(4)NHSO(4) in chloroform in phase-transfer conditions afforded a novel derivative through the initial retro-aldol fragmentation of the 8,9 bond, followed by further transformation of the intermediate aldehyde. NMR, MS and quantum chemical calculations showed that the novel compound is the acyclic oligomycin A derivative, in which the 8,9 carbon bond is disrupted and two polyfunctional branches are connected with spiroketal moiety in positions C-23 and C-25. The tri-O-acetyl derivative of the novel derivative was prepared. The acyclic oligomycin A derivative retained the ability to induce apoptosis in tumor cells at low micromolar concentrations, whereas its antimicrobial potencies decreased substantially. The derivative virtually lost the inhibitory activity against F(0)F(1) ATP synthase-containing proteoliposomes, strongly suggesting the existence of the target(s) beyond F(0)F(1) ATP synthase that is important for the antitumor potency of oligomycin A.

• Authors: Lyudmila N Lysenkova, Konstantin F Turchin, Alexander M Korolev, Evgenyi E Bykov, Valery N Danilenko, Olga B Bekker, Alexey S Trenin, Sergei M Elizarov, Lyubov G Dezhenkova, Alexander A Shtil, Maria N Preobrazhenskaya
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 65 Issue 8 Pg. 405-11 (Aug 2012) ISSN: 1881-1469 [Electronic] England
• PMID: 22617550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antineoplastic Agents
• Enzyme Inhibitors
• Oligomycins
• ATP Synthetase Complexes

Topics

• ATP Synthetase Complexes (antagonists & inhibitors, metabolism)
• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (physiology)
• Cell Survival (drug effects)
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• HCT116 Cells
• Humans
• K562 Cells
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Oligomycins (chemical synthesis, chemistry, pharmacology)
• Spectrometry, Mass, Electrospray Ionization
• Spectrophotometry, Infrared
• Spectrophotometry, Ultraviolet