Screening and evaluation of fungal resources for loratadine metabolites

摘要

Loratadine is a selective inverse agonist of peripheral histamine H1-receptors. Microbial biotransformation gained a lot of attention for its ability to convert molecules to valuable medicinally active substances. The main objective of the present research was to investigate the ability of different fungi to biotransform the drug loratadine to its active metabolite desloratadine, because desloratadine is four times more potent, possess longer duration of action than loratadine and is effective at low doses. The screening studies were performed with selected fungi using their respective broth media and sterile incubation conditions. The drug and metabolites formed (if any) were extracted and analysed using HPLC analysis. Structural elucidation and confirmation of metabolites were by mass and proton NMR spectroscopy. Among the six fungi selected, Cunninghamella elegans, Cunninghamella echinulata and Aspergillus niger cultures showed extra peaks at 3.8, 3.6 and 4.1 min, respectively, in HPLC when compared with their controls, which indicated the formation of metabolites. The metabolites thus formed were isolated and their structures were confirmed as dihydroxy desloratadine, desethoxy loratadine and 3-hydroxy desloratadine by Cunninghamella elegans, Cunninghamella echinulata and Aspergillus niger cultures, respectively, by mass spectrometry and NMR spectroscopy. Three fungi were identified to have the ability to biotransform loratadine to its active metabolite and other different metabolites.