Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Inhibition of human glutathione transferase P1-1 by novel benzazole derivatives
Hacettepe University, Turkey.ORCID iD: 0000-0003-0999-3179
Show others and affiliations
2012 (English)In: Türk Biyokimya Dergisi, ISSN 0250-4685, E-ISSN 1303-829X, Vol. 37, no 4, 431-436 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Glutathione transferases (GST) are multifunctional enzymes involved in detoxication, drug resistance, cell signaling and apoptosis. The inhibitory effects of novel benzazole derivatives were tested on human GST P1-1 to find new agents for overcoming drug resistance in cancer cells. Methods: GST P1-1 was heterogously expressed in E. coli strain XL-1 Blue and purified using S-hexylglutathione-Sepharose 6B affinity chromatography. The effect of 33 potential inhibitors on enzymatic activity was assayed spectrophotometrically with 1-chloro-2,4-dinitrobenzene (CDNB) as well as with the alternative substrate phenethyl isothiocyanate (PEITC). Results: Compound-18(N-[2-(4-chloro-benzyl)-benzooxazol-5-yl]-4-nitro-benzenesulfonamide) was the most potent inhibitor found with an IC50 value of approximately 10 mu M with respect to CDNB and a somewhat less strong inhibitor (45 % inhibition at 40 mu M) with PEITC as substrate. Compound-18 showed mixed inhibition with GSH and uncompetitive inhibition with CDNB with the K-i values 6.3 +/- 0.7 mu M and 11.8 +/- 3.4 mu M, respectively. Conclusion: Compound-18 is a potent inhibitor of GST P1-1. It may serve as a lead for further chemical modifications for increased potency. Additional studies will elucidate the effects of the inhibitor on cancer cells.

Place, publisher, year, edition, pages
2012. Vol. 37, no 4, 431-436 p.
Keyword [en]
GST P1-1, enzyme inhibition, benzazole derivatives, anti-cancer drugs
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-88375DOI: 10.5505/tjb.2012.30301ISI: 000314289700013OAI: oai:DiVA.org:su-88375DiVA: diva2:611264
Note

AuthorCount:8;

Available from: 2013-03-15 Created: 2013-03-13 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Musdal, YamanMannervik, Bengt
By organisation
Department of Neurochemistry
In the same journal
Türk Biyokimya Dergisi
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 42 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf