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). We have synthesized ethylthioribose (ETR), a water-soluble, acid-stable analog of the naturally-occurring compound methylthioribose. In preliminary experiments, we have found that ETR: 1) is cytocidal to Candida albicans in vitro, 2) has no effect on the growth of mammalian cells in vitro, and 3) has no apparent adverse effects on mice when administered intraperitoneally or intravenously. Our long term objective is to develop effective and non-toxic antifungal/antimicrobial agents.
The specific aims of 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, if any, of ETR in mice, and 3) determine the antimicrobial spectrum of ETR against a wide variety of clinical isolates. The development of a non-toxic antifungal agent will allow early therapeutic intervention in patients with suspected fungal infections as well as prophylactic treatment in immunocompromised patients.
