Inhibitors of 2,3-oxidosqualene lanosterol-cyclase as potential antifungal agents.

Fig. 1. StcJrol hiosynthesis squalene to lanosterol. This enzyme has been shown to hc essential f o r fungi; Sacchurornyces cerevisiue mutants lacking this key enzyme in fact require exogenous ergosterol supplementation for growth 121. Even if these early steps in sterol biosynthesis are common to mammals and fungi, the example of the allylamines. which act on squalene epoxidase 131. shows that a selective inhibition of fungal enzymes is possible. It has also been shown that some inhibitors of 2.3-oxidosqualene lanosterol-cyclasc differently affect fungal and mammalian enzymes 141. In the aearch for new antifungals with a differcnt mode of action, we therefore decided t o turn o u r attention t o the enzyme 2,3-oxidosqualene lanosterol-cyclase. To monitor the impact o f our synthetic inhibitors on various systems, different assays were established: