SYNTHESIS AND BIOLOGICAL-ACTIVITY OF AZASQUALENES, BIS-AZASQUALENES AND DERIVATIVES

Azasqualenes, bis-azasqualenes and derivatives, designed as inhibitors of squalene 2,3-epoxide cyclase, a key enzyme in sterol biosynthesis, were synthesized and their in vitro activities against a variety of yeasts, fungi, gram-positive and gram-negative bacteria were determined. The synthesis involves a new method of squalene degradation, together with an unusual procedure for the aminative reduction of lipophilic aldehydes. A study of the structure-activity relationship was attempted for different biological parameters: anti-bacterial and anti-fungal activities (MIC), inhibition of mycelial growth (GTT), surfactant activity (CMC) and membrane perturbation activity (induction of leakage in liposomes). © 1987.