Antileishmanial activity of hamycin: a polyene antibiotic

Hamycin, a polyene antibiotic, now in extensive use in the treatment of candidiasis and otomycosis, is found to be remarkably effective in killing Leishmania donovani promastigotes in a liquid medium at a concentration of 0.2 microgram/ml. The glucose stimulated respiration and the uptake of 2-deoxy-D[U-14C]-glucose was inhibited in cells treated with the drug at a growth inhibitory concentration. An immediate release of isotopic glucose from preloaded cells could be demonstrated after exposure to hamycin. All the above effects could be effectively prevented in the presence of ergosterol. The primary site of action of hamycin on L. donovani promastigote cells appears to be membrane sterols that result in the loss of the permeability barrier to small metabolites. The lower minimum inhibitory concentration of hamycin compared to other established drugs warrants further study in the context of increasing reports of clinical resistance to pentavalent antimonials.