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Fungal Biotransformation of Clobazam–Induction, Inhibition and Kinetic Studies


Affiliations
1 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupathi 517 502, India
 

The present study was aimed to explore the ability of six distinct fungi to biotransform the drug clobazam to its metabolites, and the nature of enzymes involved in such fungal biotransformation by performing screening, induction, inhibition and kinetic studies. Among the six organisms, a sample of Aspergillus fumigatus culture showed an extra peak at 3.5 min in the high performance liquid chromatography chromatogram when compared with its controls, indicating the formation of metabolite. The metabolite thus formed was confirmed by mass spectrometry and NMR spectroscopy as 4-hydroxy norclobazam. Enzyme induction and inhibition studies were conducted on the involvement of a CYP3A4-like enzyme in fungal biotransformation. Enzyme kinetic studies were conducted to determine the affinity of the enzyme to the substrate. The study revealed that A. fumigatus can be used as a microbial resource to analyse the complete metabolic profile of clobazam with a maximum concentration 30 μg/ml.

Keywords

Aspergillus Fumigatus, Biotransformation, Induction, Inhibition, Kinetics.
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  • Fungal Biotransformation of Clobazam–Induction, Inhibition and Kinetic Studies

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Authors

M. Keerthana
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupathi 517 502, India
M. Vidyavathi
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupathi 517 502, India

Abstract


The present study was aimed to explore the ability of six distinct fungi to biotransform the drug clobazam to its metabolites, and the nature of enzymes involved in such fungal biotransformation by performing screening, induction, inhibition and kinetic studies. Among the six organisms, a sample of Aspergillus fumigatus culture showed an extra peak at 3.5 min in the high performance liquid chromatography chromatogram when compared with its controls, indicating the formation of metabolite. The metabolite thus formed was confirmed by mass spectrometry and NMR spectroscopy as 4-hydroxy norclobazam. Enzyme induction and inhibition studies were conducted on the involvement of a CYP3A4-like enzyme in fungal biotransformation. Enzyme kinetic studies were conducted to determine the affinity of the enzyme to the substrate. The study revealed that A. fumigatus can be used as a microbial resource to analyse the complete metabolic profile of clobazam with a maximum concentration 30 μg/ml.

Keywords


Aspergillus Fumigatus, Biotransformation, Induction, Inhibition, Kinetics.

References





DOI: https://doi.org/10.18520/cs%2Fv118%2Fi4%2F603-611