Synthetic modification of manzamine A via Grubbs metathesis. Novel structures with enhanced antibacterial and antiprotozoal properties.

Abstract

A strategy for the structural modification of biologically important alkene-containing natural products via ring-opening olefin metathesis is described. Exposure of manzamine A 1 to the second-generation Grubbs catalyst in the presence of ethylene leads to the formation of 2 and 4. The antibacterial activity of the novel manzamine analogue 2 (IC50=0.10 nM) against Mycobacterium intracellulare is ca. 2-fold more potent than that of ciprofloxacin (IC50=0.18 nM), a drug that is frequently used against antibiotic-resistant infections.

• Authors: Jeffrey D Winkler, Allyn T Londregan, Mark T Hamann
• Journal: Organic letters (Org Lett) Vol. 9 Issue 22 Pg. 4467-9 (Oct 25 2007) ISSN: 1523-7060 [Print] United States
• PMID: 17918854 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antiprotozoal Agents
• Carbazoles
• manzamine A

Topics

• Animals
• Anti-Bacterial Agents (chemical synthesis, pharmacology)
• Antiprotozoal Agents (chemical synthesis, pharmacology)
• Carbazoles (chemical synthesis)
• Inhibitory Concentration 50
• Leishmania donovani (drug effects)
• Molecular Structure
• Mycobacterium avium Complex (drug effects)
• Plasmodium falciparum (drug effects)