Synthetic modification of manzamine A via Grubbs metathesis. Novel structures with enhanced antibacterial and antiprotozoal properties.
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.
Winkler
Jeffrey D
JD
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. winkler@sas.upenn.edu
Londregan
Allyn T
AT
Hamann
Mark T
MT
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D015394:Molecular Structure; D015269:Mycobacterium avium Complex / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D002227:Carbazoles; C078290:manzamine A