ETHYLTHIORIBOSE: A NEW ANTIFUNGAL AGENT

THE INCIDENCE OF FUNGAL INFECTIONS HAS INCREASED MARKEDLY SINCE THE ADVENT OF BROAD-SPECTRUM ANTIBIOTICS, CORTICOSTEROIDS, CANCER CHEMOTHERAPY, AND ORGAN TRANSPLANTATION. CURRENTLY AVAILABLE ANTIFUNGAL AGENTS SUCH AS AMPHOTERICIN B ARE OFTEN AVOIDED CLINICALLY BECAUSE OF THEIR SEVERE TOXIC SIDE EFFECTS (E.G., NEPHROTOXICITY). EPITOPE, INC. HAS SYNTHESIZED ETHYLTHIORIBOSE (ETR), A WATER-SOLUBLE, ACID-STABLE ANALOG OF THE NATURALLY OCCURRING COMPOUND METHYLTHIORIBOSE. IN PRELIMINARY EXPERIMENTS, ETR HAS BEEN FOUND TO: (1) BE CYTOCIDAL TO CANDIDA ALBICANS IN VITRO, (2) HAVE NO EFFECT ON THE GROWTH OF MAMMALIAN CELLS IN VITRO, AND (3) HAVE NO APPARENT ADVERSE EFFECTS ON MICE WHEN ADMINISTERED INTRAPERITONEALLY OR INTRAVENOUSLY. THE LONG-TERM OBJECTIVE IS TO DEVELOP EFFECTIVE AND NONTOXIC ANTIFUNGAL/ANTIMICROBIAL AGENTS. THE SPECIFIC AIMSOF THIS PHASE OF THE PROJECT ARE TO: (1) DETERMINE THE IN VIVO EFFICACY OF ETR IN A MOUSE MODEL OF SYSTEMIC CANDIDIASIS, (2) DETERMINE THE TOXICITY OF ETR IN MICE, AND (3) DETERMINE THE ANTIMICROBIAL SPECTRUM OF ETR AGAINST A WIDE VARIETY OF CLINICAL ISOLATES. THE DEVELOPMENT OF A NONTOXIC ANTIFUNGAL AGENT WILL ALLOW EARLY THERAPEUTIC INTERVENTION IN PATIENTS WITH SUSPECTED FUNGAL INFECTIONS AS WELL AS PROPHYLACTIC TREATMENT IN IMMUNOCOMPROMISED PATIENTS.