Biotransformation of tri-substitued methoxyamphetamines by Cunninghamella echinulata

By Foster, B.C. - McLeish, J. - Wilson, D.L. - Whitehouse, L.W. - Zamecnik, J. - Lodge, B.A.

Four trimethoxyamphetamine analogues were incubated with the filamentous fungus Cunninghamella echinulata. 2,4,5-Trimethoxyamphetamine and 2,5-dimethoxy-4-ethoxyamphetamine were poorly metabolized by C. echinulata ATCC 9244 and C. echinulata var. elegans ATCC 9245. 2,5-Dimethoxy-4-(n)-propoxyamphetamine was mainly metabolized through N-acetylation and O-dealkylation with minor amounts of several aliphatic hydroxylation metabolites formed. 2,5-Dimethoxy-4-methylthioamphetamine was extensively metabolized to the corresponding sulphoxide. 2,5-Dimethoxy-4-methylthioamphetamine metabolism was inhibited by ethanol and quinidine. Sparteine did not inhibit the formation of the sulphoxide and may have shunted the substrate through alternate metabolic pathways. Incubation conditions can affect the rate and extent of fungal biotransformation of 2,5-dimethoxy-4-methylthioamphetamine, and influence dextrose utilization, ammonia formation and pH.