Microbial Transformation of Pimavanserin by Cunninghamella blakesleeana AS 3.970

Pimavanserin is an approved selective 5-HT2A receptor inverse agonist for treating Parkinson’s disease psychosis. However, few studies on its metabolism in vitro have been investigated. In this research, eight strains of fungi are used to study the pimavanserin profiles and six them demonstrated positive transformation results. Factors influencing rate, like substrate concentration, culture time, initial media pH value, temperature, shaking speed, were evaluated optimized. Cunninghamella blakesleeana AS3.970 provided best rate 30.31%, 10 unreported metabolites screened by LC-MS/MS. Among these metabolites, M1 major one identified as 1-(4-fluorobenzyl)-3-(4-(2-hydroxy-2-methylpropoxy)benzyl)-1-(1-methylpiperidin-4-yl)urea, which a hydroxylation product pimavanserin. A preliminary molecular docking simulation was performed, indicated that exhibits similar binding properties with may become potential candidate treatment.