# Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum
> Subehan

URL kanonis: https://discover.unhas.ac.id/publications/pub_scopus_33744913556
Jurnal / Konferensi: Planta Medica
Tahun terbit: 2006
DOI: https://doi.org/10.1055/s-2006-931558
ISSN: 00320943
Kuartil SJR: Q2
Citations: 39

## Authors
- Subehan

## Abstract
Nineteen alkamides isolated from Piper nigrum L. were tested for their mechanism-based inhibition on human liver microsomal dextromethorphan O-demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6). All compounds increased their inhibitory activity with increasing preincubation time. Among them, 15 and 17 showed more than 50 % decrease of the CYP2D6 residual activity after 20 min preincubation. Further investigations on 15 and 17 showed that the characteristic time- and concentration-dependent inhibition, which required a catalytic step with NADPH, was not protected by nucleophiles, and was decreased by the presence of a competitive inhibitor. The kinetic parameters for inactivation (kinact and KI) were 0.028 min-1 and 0.23 microM for 15 and 0.064 min-1 and 0.71 microM for 17, respectively, which were stronger than the known mechanism-based inhibitor, paroxetine (a positive control). Thus, 15 and 17 are potent mechanism-based inhibitors of CYP2D6.

## Keywords
- Dextromethorphan
- Microsome
- CYP2D6
- Cytochrome P450
- Chemistry
- Non-competitive inhibition
- Demethylation
- Pharmacology
- Mechanism of action
- Piper
- Enzyme
- Stereochemistry
- Biochemistry
- Biology
- Medicine
- In vitro
- Traditional medicine
- Gene expression
- DNA methylation
- Gene

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Sumber: Discover Unhas — RIMS Universitas Hasanuddin.
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