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Updated: Jul 7, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Structure-activity relationships for the inhibition of recombinant human cytochromes P450 by curcumin analogues
Regina Appiah-Opong1, Iwan de Esch, Jan N M Commandeur
1Divisions of Molecular Toxicology, Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands.
Abstract:
Inhibition of cytochrome P450 (CYP) is a major cause of drug-drug interactions. In this work, inhibitory potentials of 33 curcumin analogues, i.e. 2,6-dibenzylidenecyclohexanone (A series), 2,5-dibenzylidenecyclopentanone (B series) and 1,4-pentadiene-3-one (C series) substituted analogues of curcumin towards recombinant human CYP1A2, CYP3A4, CYP2B6, CYP2C9 and CYP2D6, all important for drug metabolism, were studied in vitro. Fluorescence plate reader and high performance liquid chromatography (HPLC) assays were used to evaluate CYP-inhibitory activities. MOE-based Quantitative structure-activity relationship (QSAR) analysis suggested that electrostatic and hydrophobic interactions and lipophilicity are important factors for CYP inhibition. Apart from insights in important molecular properties for CYP inhibition, the present results may also guide further design of curcumin analogues with less susceptibility to drug-drug interactions.
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