10-Phenyltriazoyl Artemisinin is a Novel P-glycoprotein Inhibitor that Suppresses the Overexpression and Function of P-glycoprotein

Current Pharmaceutical Design
Dong-Hwan LeeSo Won Kim

Abstract

The effect of drugs on ATP-binding cassette transporters, especially permeabilityglycoprotein (P-gp), is an important consideration during new anti-cancer drug development. In this context, the effects of a newly synthesized artemisinin derivative, 10-(4-phenyl-1H-1,2,3- triazol)-artemisinin (5a), were evaluated on P-gp expression and function. Reverse transcript polymerase chain reaction and immunoblotting techniques were used to determine the effect of 5a on P-gp expression in LS174T cells. In addition, the ability of 5a to work as either a substrate or an inhibitor of P-gp was investigated through different methods. The results revealed that 5a acts as a novel P-gp inhibitor that dually suppresses the overexpression and function of P-glycoprotein. Co-treatment of LS174T cell line, human colon adenocarcinoma cell line, with 5a and paclitaxel recovered the anticancer effect of paclitaxel by controlling the acquired drug resistance pathway. The overexpression of P-gp induced by rifampin and paclitaxel in a colorectal cell line was suppressed by 5a which could be a novel inhibitory substrate inhibiting the transport of paclitaxel by P-gp. The results revealed that 5a can be classified as a type B P-gp inhibitor (with both substr...Continue Reading

References

Jan 31, 2002·Annual Review of Medicine·Michael M Gottesman
Dec 25, 2002·Biological & Pharmaceutical Bulletin·Paiboon Reungpatthanaphong, Samlee Mankhetkorn
Jul 19, 2003·Molecular Pharmacology·Thomas EfferthJens Oliver Funk
Oct 14, 2003·Bioorganic & Medicinal Chemistry Letters·Sangtae OhSeokjoon Lee
Jun 24, 2004·Bioorganic & Medicinal Chemistry·Sangtae OhSeokjoon Lee
Mar 7, 2006·Nature Reviews. Drug Discovery·Gergely SzakácsMichael M Gottesman
Apr 14, 2007·Mini Reviews in Medicinal Chemistry·Seokjoon Lee
Jul 13, 2007·Nature
Nov 24, 2007·Journal of Chemical Information and Modeling·Peter ErtlAnsgar Schuffenhauer
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S-F Zhou
Sep 2, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Oliver von RichterKarl Zech
Jun 10, 2010·Nanomedicine·Xiaowei Dong, Russell J Mumper
Oct 29, 2010·Acta Biochimica Et Biophysica Sinica·Yaxin ZhaoWei Jin
Jan 25, 2012·Journal of Toxicologic Pathology·Robert A EttlinDavid E Prentice
Apr 13, 2012·Expert Opinion on Investigational Drugs·Marco Falasca, Kenneth J Linton
Sep 1, 2012·Investigational New Drugs·Henry C LaiTomikazu Sasaki
Apr 2, 2013·FEBS Letters·Peter Andorfer, Hans Rotheneder
Apr 11, 2015·Annals of Medical and Health Sciences Research·A K Das
Mar 20, 2018·Emerging Infectious Diseases·Mie IkedaToshihiro Mita
Apr 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lisa GruberThomas Efferth

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Citations

Mar 11, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Tuyelee DasAbhijit Dey
Feb 12, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bowen LiHangyu Li

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