PRADIMICINS - A NOVEL CLASS OF BROAD-SPECTRUM ANTIFUNGAL COMPOUNDS

Pradimicins are a new class of antifungal compounds currently undergoi ng preclinical and early phase I clinical trials. The pradimicin struc ture is characterized by an aglycone of dihydrobenzo (alpha) napthacen equinone with substitutions by a D-amino acid and hexose sugar. Pradim icins possess a novel mechanism of action consisting of a specific bin ding recognition to terminal D-mannosides of the cell wall of Candida albicans, resulting in the formation of a ternary complex consisting o f D-mannoside, pradimicin, and calcium that leads to disruption of the integrity of the fungal cell membrane. Pradimicin in the form of BMS- 181184 has broad-spectrum in vitro antifungal activity against Candida spp., Cryptococcus neoformans, Aspergillus spp., dematiaceous molds, and the Zygomycetes. Fusarium spp. are comparatively resistant to high concentrations of pradimicin. Initial in vivo studies indicate that p radimicins have antifungal activity against experimental murine dissem inated candidiasis and disseminated aspergillosis. Early studies indic ate an excellent therapeutic index with no major end-organ toxicity. P radimicins warrant further investigation for treatment of opportunisti c mycoses in immuno-compromised hosts.