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Inhibiton of CYP 3A4 with novel synthetic coumarin and flavanone analogs
Author(s) -
Swift David Aaron,
Hopkins Nancy
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.967.4
Subject(s) - chemistry , cyp3a4 , cytochrome p450 , pharmacology , coumarin , flavanone , drug , microsome , pharmacokinetics , in vitro , enzyme , biochemistry , ic50 , flavonoid , antioxidant , medicine , organic chemistry
Human Cytochrome P450 3A4 (CYP 3A4) is an oxidative enzyme found in hepatocytes and enterocytes and is a key agent in the metabolism of pharmaceutical drugs. CYP 3A4 is very important in the understanding of drug interaction and drug efficiency with implications in the fields of pharmacokinetics and chemotherapy. Novel synthetic analogs of a variety of Flavanones and Coumarins will be screened to test their ability to inhibit CYP 3A4 in vitro. These compounds are analogs of natural dietary products that have shown efficacy in inhibiting 3A4 or of compounds that have proven methods of inhibition in other non‐hepatic and enteroceullar p450's. The IC50 of these compounds will be tested using a rapid assay on a known flourocoumarin substrate. Then a 96 well fluorescence plate reader and computer analysis will be used to test the degree of inhibition each substance has on the substrate. By altering CYP 3A4 activity we can manipulate the amount of time drugs stay in tissue. This is particularly important with certain chemotherapy drugs that have high metabolic rates. In inhibiting CYP 3A4 we can increase the amount of time that these drugs work in tissue.