In vitro assessment of cytotoxicity and biotransformation of propranolol in Cunninghamella echinulata

By Foster, B.C. - Litster, D.L. - Wilson, D.L. - Ormsby, E. - Dawson, B.A.

Biotransformation studies with five concentrations of racemic propranolol were conducted using the filamentous fungus Cunninghamella echinulata ATCC 9244. The rate of formation and subsequent disappearance of a new major metabolite, 8-hydroxypropranolol, was dose-dependent. Desisopropylpropranolol and 4-hydroxy-propranolol were also formed. 4-Hydroxypropranolol was the major fungal metabolite in earlier studies. Propranolol exerted a dose-dependent response on biotransformation, fungal growth, dextrose utilization, ammonia formation and incubation broth pH. Determination of dextrose utilization and incubation broth pH would provide reliable, cost-effective and convenient alternative methods for cytotoxicological evaluation.