The goal of this project is to study the antifungal agents present in higher plant extracts in order to discover agents with novel structures and novel modes of action and to determine their potential for use in the treatment of human fungal diseases. Higher plants have been demonstrated in preliminary studies frequently to have antifungal activity. Some of the active plants have a prior folkloric reputation for treatment of fungal infections. Other have activity broad enough to include human pathogens. Novel antifungal agents are especially sought for the treatment of contemporarily troublesome diseases against which current fermentation- based antifungals are not fully satisfactory for reasons of toxicity, low potency, resistance, poor pharmacokinetic characteristics, and the like. Central to this effort is the obtention and botanical identification of suitable plant material, extraction, screening against mechanism-based enzyme assays and a battery of disease indicator fungi, bioassay directed fractionation, physico-chemical structure determination, synthesis (where indicated for structural clarification, preparation of substantial quantities,l optimization of structure-activity relationships, etc.), evaluation of in vitro antifungal spectrum and potency in comparison with established antifungals and in vivo evaluation in infected experimental animals.
| Shen, L L; Fostel, J M (1994) DNA topoisomerase inhibitors as antifungal agents. Adv Pharmacol 29B:227-44 |
| Shen, L L; Baranowski, J; Fostel, J et al. (1992) DNA topoisomerases from pathogenic fungi: targets for the discovery of antifungal drugs. Antimicrob Agents Chemother 36:2778-84 |
| Fostel, J M; Montgomery, D A; Shen, L L (1992) Characterization of DNA topoisomerase I from Candida albicans as a target for drug discovery. Antimicrob Agents Chemother 36:2131-8 |
