Abstract
The molecular and electronic structural characteristics of the hepatotoxic and phototoxic antirheumatic drug, benoxaprofen, indicate that it falls in the interface between the area of parametric space associated with substrates of cytochrome P450I and that associated with substrates of other cytochromes P450, combining fairly planar molecular geometry (area/depth 2 = 2.5) with relatively low activation energy ( ΔE = E(LEMO) − E(HOMO) = 12.0). Benoxaprofen may therefore be a substrate for cytochrome P450I so that, like many other P450I substrates, it may be oxygenated to a reactive intermediate, thereby causing hepatotoxicity. Benoxaprofen also has a molecular structure closely similar to that of clofibrate and may thus be a possible substrate for cytochrome P450IV and result in hepatic peroxisomal proliferation. The structural similarity of benoxaprofen with the furocoumarin, psoralen, is associated with its known phototoxicity. QSAR analysis of the acute toxicities and anti-inflammatory activities of 16 analogues of benoxaprofen has been undertaken to identify a drug candidate likely to have similar anti-inflammatory activity to benoxaprofen but with lower toxicity.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.