Sordarin antifungal agents

Sordarins are natural products from a range of different producer fungi tha t show antifungal activity. Results from studies with a series of semi-synt hetic sordarin derivatives from Glaxo Wellcome indicates the molecules show potential for broad spectrum activity, with a high antifungal specificity based on the nature of their interaction with protein elongation factor 2. Several of the compounds have demonstrated efficacy by sc. or oral administ ration in mouse models of Candida albicans, Histoplasma capsulatum. Coccidi oides immitis and Pneumocystis carinii infection and early toxicological st udies show no serious potential for adverse effects. However, the t(1/2) of the compounds in several animal species is very short, suggesting that hig h and repeated dosing may prove to be necessary for management of some seri ous fungal diseases. Patents for sordarin antifungals and for their target have been published principally from Glaxo Wellcome and from Merck & Co. Ho wever, Glaxo Wellcome has now terminated their own development programme fo r the agents and no details are yet available to indicate a candidate for c linical development will soon appear from Merck. The sordarins offer intere sting potential thanks to the novelty of their mode of action: they may req uire substantially more research to reveal an ideal candidate for clinical development.