Naslov
SCREENING OF FLAVONOIDS AS POTENTIAL CYTOCHROME P450 3A4 INHIBITORS

Autori
Bojić, Mirza

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
9th World Congress on Polyphenols Application / Edeas, Marvin - St. Julian's : International Society of Antioxidants, 2015, 23-23

ISBN
978-2-35609-073-7

Skup
9th World Congress on Polyphenols Application

Mjesto i datum
San Ġiljan, Malta, 03.06.2015. - 05.06.2015

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
CYP3A4; flavonoids

Sažetak
Enzyme cytochrome P450 3A4 metabolizes the greatest number of xenobiotics and it could be expected that some flavonoids have potential of inhibiting this enzyme and consequently can cause interactions with other drugs. The objective of this work was to screen flavonoids as potential cytochrome P450 3A4 inhibitors and determine a type of inhibition. A set of thirty flavonoids was selected for screening (3 μM). Each flavonoid was preincubated with recombinant cytochrome P450 3A4 for half an hour with NADPH. Residual activity was determined by adding marker substrate - testosterone. Relative change in production of 6β-hydroxytestosterone compered to the control was determined by HPLC (1). Time-dependent inhibition and direct inhibition was also tested. Out of thirty flavonoids tested seven flavonoids have shown metabolism dependent inhibition, three time-dependent inhibition and three direct inhibition. Most prominent metabolism dependent inhibitor of cytochrome P450 3A4 was acacetin that decreased residual activity by 95% (p=0.007) of which 54% (p=0.005) could be attributed to direct inhibition. The results obtained suggest that some flavonoids can inhibit cytochrome P450 3A4 in concentration that can be achieved in vivo. Further studies are needed to determine inhibition kinetic parameters, and in case of metabolism dependent inhibition possible mechanism of inactivation.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA