Propranolol Metabolism byCunninghamella Bainieri

Abstract

1. Incubations of racemic propranolol alone or in the presence of either quinidine or sparteine were performed with Cunninghamella bainieri. 2. Five mammalian metabolites of propranolol (4-hydroxypropranolol, desisopropyl-propranolol, 1-naphthoxylactic acid, propranolol glycol and 1-naphthoxyacetic acid) were present in unhydrolysed extracts of the incubation medium according to h.p.l.c. and g.l.c. analyses. The relative proportion of 4-hydroxypropranolol increased after enzymic treatment. 3. Propranolol not only had a fungistatic effect, but also caused morphological changes in the organism, which were accompanied by decomposition of 4-hydroxypropranolol and formation of a greenish-brown colour in the incubation medium. 4. Drug interaction experiments yielded results which paralleled those reported in mammals. 5. The findings indicate that C. bainieri may be a useful microbial model for drug disposition and interaction studies.

Use of microorganisms for the study of drug metabolism: An update

“…In particular, it was noted that the level of dextrose in a trypticase soy broth affected the nature of metabolites produced by the fungus. 63 The five mammalian metabolites of propranolol (64-68) were all detected at some level as metabolites of C. bainieri as well. Of these five, the major metabolite was the expected Chydroxypropranolol (64).…”

“…It was speculated that this effect may be similar in mechanism to the sperm antimotility effects of this drug which have been attributed to the accumulation of glycolytic intermediates of propranolol in the sperm cell membrane. 63 Foster and co-workers also investigated the biotransformation of a series of aryl-alkylamines by the fungus Cunninghamella bainieri.% Citing the common occurrence of aryl-alkylamines in therapeutic agents and the absence of a prospective evaluation of the effects of simple structural modifications on the metabolism of such agents by fungi, these investigators undertook a study of the metabolism of a series of phenylethylamines by C. &uinieri.& PhenyIethylamines are generally metabolized in mammalian systems by six major routes: ring hydroxylation; aliphatic hydroxylation; oxidative deamination; N-oxidation; N-dealkylation; conjugation. The nature of the mammalian metabolic products is species dependent and is affected by factors such as lipophilicity and the steric hindrance of the N-alkyl and a-carbon substituents.…”

Bioremediation of PCP by Trichoderma and Cunninghamella Strains Isolated from Sawdust

“…Different from Trichoderma species, however, Cunninghamella species have been used widely as a microbial model of mammalian metabolism of various pharmaceutical drugs and xenobiotics due to their ability to metabolise these compounds in a manner similar to that in the mammals (Abourashed et al 1999;Asha and Vidyavathi 2009). Several species of this zygomycetes, normally found in the soil such as Cunninghamella elegans, Cunninghamella blakesleeana and C. bainieri have been used to oxidize, transform or metabolize various drugs (propranolol, warfarin, naproxen, verapamil and flutamide), phenylurea herbicide (chlortoluron, diuron and isoproturon) and organopollutants such as poly aromatic hydrocarbons (anthracene, phenanthrene and fluorine) (Ferris et al 1973;Cerniglia and Yang 1984;Foster et al 1989;Rizzo and Davis 1989;Vroumsia et al 1996;Garon et al 2000;Zhong et al 2003;Sun et al 2004;Amadio and Murphy 2011). Cunninghamella species have also been reported to degrade organochlorine such as PCP (Seigle-Murandi et al 1992).…”

Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

“…12 The fungus Cunninghamella bainieri biotransformed Prop to 4-OH-Prop and the metabolites desisopropylpropranolol, propranolol glycol, 1-naphthoxylactic acid and 1-naphthoxyacetic acid were also found in trace amounts. C. echinulata was also used to biotransform Prop, 13 but the observed profile was different because the major metabolite formed was identified as 8-hydroxypropranolol.…”