ABSTRACT
One new and one known isoflavan, 3 S(+)-7-methoxymanuifolin K (1) and manuifolin K (2), respectively, were isolated from methanolic extracts of Dalea aurea (Fabaceae). Isoflavans 1 and 2 exhibited significant in vitro activity against the ameba Naegleria fowleri, an organism responsible for an infrequent but rapidly fatal form of primary amebic meningoencephalitis (PAM). At concentrations of 30 microM, both 1 and 2 caused growth inhibition of N. fowleri at a level comparable to amphotericin B (at 0.1 microM), the currently preferred treatment for this disease. Over a seven-day growth period, 1 and 2 (30 microM) exhibited superior growth inhibition of N. fowleri than amphotericin B after day 4. Isoflavan 2 was evaluated in a mouse model of PAM at a dose of 25 mg/kg/day for five days. While amphotericin B (2.5 mg/kg/day) offered 12.5 % protection of the mice, compound 2 did not protect the mice from PAM infection compared to controls.
Subject(s)
Amebicides/pharmacology , Amoeba/drug effects , Central Nervous System Protozoal Infections/drug therapy , Fabaceae , Phytotherapy , Plant Extracts/pharmacology , Amebicides/administration & dosage , Amebicides/therapeutic use , Animals , Disease Models, Animal , Isoflavones/administration & dosage , Isoflavones/pharmacology , Isoflavones/therapeutic use , Male , Meningoencephalitis/drug therapy , Mice , Mice, Inbred Strains , Opportunistic Infections/drug therapy , Parasitic Sensitivity Tests , Plant Extracts/administration & dosage , Plant Extracts/therapeutic useABSTRACT
This is a follow-up report on the viability of pathogenic Naegleria fowleri, Naegleria australiensis and Acanthamoeba castellanii isolates during 5 to 10 years of cryopreservation at -70 degrees C. The greatest decrease in viability occurred with N. fowleri and the least occurred with N. australiensis. At 10 years of cryostorage, viability was 21% for N. fowleri, 32% for A. castellanii and 51% for N. australiensis.
