title: Antitumor benzothiazoles. 26.(1) 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines.
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 (GI(50) < 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.
authors.affiliation: Cancer Research UK Experimental Cancer Chemotherapy Research Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, UK.
authors.forename: Catriona G
authors.initials: CG
authors.lastname: Mortimer
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Wells
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Crochard
authors.forename: Erica L
authors.initials: EL
authors.lastname: Stone
authors.forename: Tracey D
authors.initials: TD
authors.lastname: Bradshaw
authors.forename: Malcolm F G
authors.initials: MF
authors.lastname: Stevens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westwell
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: C507816:2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole; D000970:Antineoplastic Agents; D052160:Benzothiazoles