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Inhibition of human glutathione transferase P1-1 by novel benzazole derivatives
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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 μM with respect to CDNB and a somewhat less strong inhibitor (45 % inhibition at 40 μM) with PEITC as substrate. Compound-18 showed mixed inhibition with GSH and uncompetitive inhibition with CDNB with the Ki values 6.3 ± 0.7 μM and 11.8 ± 3.4 μM, 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]
Anti-cancer drugs, Benzazole derivatives, Enzyme inhibition, GST P1-1
National Category
Medical and Health Sciences Natural Sciences
URN: urn:nbn:se:uu:diva-195217DOI: 10.5505/tjb.2012.30301ISI: 000314289700013OAI: oai:DiVA.org:uu-195217DiVA: diva2:607093
Available from: 2013-02-21 Created: 2013-02-21 Last updated: 2013-03-04Bibliographically approved

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