Antitumor benzothiazoles. 26.2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon and breast cancer cell lines

Mortimer, C.G., Wells, G., Crochard, J.P., Stone, E., Bradshaw, T.D., Stevens, M.F.G. and Westwell, A.D. (2006) Antitumor benzothiazoles. 26.2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon and breast cancer cell lines. Journal of Medicinal Chemistry, 49 . pp. 179-185. 10.1021/jm050942k .

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DOI: 10.1021/jm050942k

Abstract

A series of new 2-phenylbenzothiazoles has been synthesized on the basis of the discovery of the potent and selective in vitro antitumor properties of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (8n; GW 610, NSC 721648). Synthesis of analogues substituted in the benzothiazole ring was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. Compounds were evaluated in vitro in four human cancer cell lines, and compound 8n was found to possess exquisitely potent antiproliferative activity (GI50 < 0.1 nM for MCF-7 and MDA 468). Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. Structure-activity relationships established that the compound 8n stands on a pinnacle of potent activity, with most structural variations having a deactivating in vitro effect. Mechanistically, this new series of agents contrasts with the previously reported 2-(4-aminophenyl)benzothiazoles; compound 8n is not reliant on induction of CYP1A1 expression for antitumor activity.

Item Type:Article
Additional Information:Full text available electronically from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:978
Journal or Publication Title:Journal of Medicinal Chemistry
Deposited By:Library Staff
Deposited On:02 Jun 2008 15:38
Last Modified:12 May 2011 17:57

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