in vitro and in silico Studies of Interaction of Synthetic 2,6,9-Trisubstituted Purine Kinase Inhibitors BPA-302, BP-21 and BP-117 With Liver Drug-Metabolizing Cytochromes P450

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F20%3A00541026" target="_blank" >RIV/61389030:_____/20:00541026 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/20:73603436

Result on the web

<a href="https://www.biomed.cas.cz/physiolres/pdf/2020/69_S627.pdf" target="_blank" >https://www.biomed.cas.cz/physiolres/pdf/2020/69_S627.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.934611" target="_blank" >10.33549/physiolres.934611</a>

Result language

angličtina

Original language name

in vitro and in silico Studies of Interaction of Synthetic 2,6,9-Trisubstituted Purine Kinase Inhibitors BPA-302, BP-21 and BP-117 With Liver Drug-Metabolizing Cytochromes P450

Original language description

An evaluation of possible interactions with enzymes of drug metabolism (cytochromes P450, CYP) is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. The article is focused on the preliminary metabolic study of selected 2,6,9-trisubstituted purine kinase inhibitors with significant anticancer activities which we have developed. The compounds BP-21 and BP-117 represent strong CDK inhibitors and the compound BPA-302 was developed as selective FLT3-ITD kinase inhibitor. Here, emphasis is placed on interactions of these compounds with the nine most important forms of CYP to evaluate the possibility of inhibition of these enzymes. The possibility of their inhibitory effect was studied in vitro on selected human liver microsomal CYP enzymes. The most affected enzyme was CYP2C19. Its activity dropped to 22 % of its original value by BPA-302, to 13 % by BP-21 and to 6 % by BP-117 at the highest concentration tested (250 mu mol.l(-1)). The results suggest that the metabolism of concomitantly administered drugs should not be significantly affected at lower doses. Molecular docking of BPA-302 indicated that it can bind to active site of both CYP2C19 and CYP2D6 enzymes above the heme cofactor corroborating the experimental data.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

1802-9973

Volume of the periodical

69

Issue of the periodical within the volume

SEP

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

10

Pages from-to

627-636

UT code for WoS article

000621838200009

EID of the result in the Scopus database

2-s2.0-85102232304