Abstract:
:The results of extensive quantitative structure-activity relationship (QSAR) analyses on 15 series of cytochrome P450 inhibitors, covering a total of 7 enzymes and 199 compounds, are reported. In general, it is found that lipophilicity represents the most important single factor in describing differences in inhibitory potency towards P450 enzymes. In two instances, this relationship is parabolic in nature but, by and large, the logarithm of inhibitory activity relates linearly with log P, where P is the octanol-water partition coefficient. On occasions, other parameters are involved in the QSAR expressions but there are many examples where either log P or its ionization-corrected equivalent, log D7.4, are the sole structural descriptors of inhibition. The correlations presented exhibit a range in R value from 0.85 to 0.99, where R is the correlation coefficient, and it is found that R is greater than 0.9 in 80% of the QSARs presented. It is apparent from these findings, therefore, that compound lipophilicity plays a major role in the ability of xenobiotics to inhibit enzymes of the cytochrome P450 superfamily, presumably due to the essentially hydrophobic nature of the active site region.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Lewis DF,Lake BG,Dickins Mdoi
10.1080/14756360600952183subject
Has Abstractpub_date
2007-02-01 00:00:00pages
1-6issue
1eissn
1475-6366issn
1475-6374journal_volume
22pub_type
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