Therapeutic target for smoking cessation : inhibition of cytochrome P450 2A6 and 2A 13 by pluchea indica plant constituents

Name: Khanishtha Prakobsri

LCSH: Burapha University.Faculty of Science

Classification :.DDC: 615.5

LCSH: Burapha University.Faculty of Engineering

LCSH: Therapeutics

Abstract: Inhibition of cytochrome P450 2A6 (CYP2A6) and cytochrome P450 2A13 (CYP2A13) enzymes had been proven to help smoking cessation and prevent lung cancer in smokers. Preliminary screening suggested that high inhibitory effect of Pluchea indica was found to against both CYP2As enzymes. This research aimed to identify and characterize the bioactive compounds from this plant against two target enzymes in vitro and in silico. In this study, three flavonoids (apigenin, luteolin and quercetin) and acetylenic thiophene 1-3 were isolated from ethyl acetate and hexane fraction, respectively. As the inhibitory activity of these flavonoids against CYP2As enzymes has been reported, this study focused mainly on the inhibitory activity of acetylenic thiophene 1-3. The results showed that thiophene 3 was the best inhibitor against both CYP2A6 and CYP2A13 with IC50 3.90 ± 0.20 μM and 2.40 ± 0.33 μM respectively. In contract, thiophene 1 was the worst inhibitor with IC50 6.43 ± 1.29 μM and 6.18 ± 0.28 μM for CYP2A6 and CYP2A13, respectively. Moreover, all of thiophene exhibited the mechanism based inhibition characteristic. Detail in silico structural-function relationship of thiophene 1-3 toward CYP2As enzymes indicated that the long chain of thiophene 1 hampered the hydrophobic interaction between the thiophene ring and specific residues in the CYP2As active sites, resulting in low inhibitory activity compared with thiophene 2 and thiophene 3. Therefore, isolated thiophene 2 and thiophene 3 from P. indica have effectively inhibited both of CYP2As enzymes and could be a candidate compound for further application in drug therapy for smoking cessation and lung cancer prevention.

Burapha University. Library

Address: CHONBURI

Email: buulibrary@buu.ac.th

Name: Songklod Sarapusit

Role: Principal advisor

Created: 2019

Modified: 2022-06-10

Issued: 2022-05-12

วิทยานิพนธ์/Thesis

application/pdf

CallNumber: Th 615.5 Kh45T

eng

DegreeName: Master of Bioengineering

Level: Master's Degree

Descipline: Bioengineering

Grantor: Burapha University

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