Journal ArticleDOI
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.
Catriona G. Mortimer,Geoffrey Wells,Jean-Philippe Crochard,Erica L. Stone,Tracey D. Bradshaw,Malcolm F. G. Stevens,Andrew D. Westwell +6 more
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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.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.read more
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The role of fluorine in medicinal chemistry
Poonam Shah,Andrew D. Westwell +1 more
TL;DR: The increasingly routine incorporation of fluorine atom(s) into drug candidates suggests a bright future for fluorine in drug discovery and development, and a major challenge moving forward will be how and where to install fluorine to best optimise molecular properties.
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The expanding role of prodrugs in contemporary drug design and development
TL;DR: This Review highlights prodrug design strategies for improved formulation and pharmacokinetic and targeting properties, with a focus on the most recently marketed prodrugs.
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Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents.
TL;DR: Five series of thiourea derivatives bearing benzothiazole moiety were efficiently synthesized and evaluated for antimicrobial and anticancer activities and showed higher activity against fungi than bacteria.
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A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry.
TL;DR: This work systematically gives a comprehensive review in current developments of BTA-based compounds in the whole range of medicinal chemistry as anticancer, antibacterial, antifungal, antiinflammatory, analgesic, anti-HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial and other medicinal agents.
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Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids
TL;DR: A detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques is offered and the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids are highlighted.
References
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A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
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Some Practical Considerations and Applications of the National Cancer Institute In Vitro Anticancer Drug Discovery Screen
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Journal ArticleDOI
Antitumor benzothiazoles. 3. Synthesis of 2-(4-aminophenyl)benzothiazoles and evaluation of their activities against breast cancer cell lines in vitro and in vivo.
Dong-Fang Shi,Tracey D. Bradshaw,Samantha Wrigley,Carol Jane Mccall,Peter Lelieveld,Iduna Fichtner,Malcolm F. G. Stevens +6 more
TL;DR: Four compounds have been evaluated in vivo against human mammary carcinoma models in nude mice and compound 9a showed the most potent growth inhibition against the ER+ (MCF-7 and BO) and ER- (MT-1 and MT-3) tumors.
Journal ArticleDOI
Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)benzothiazoles.
Ian Hutchinson,Mei-Sze Chua,Helen L. Browne,Valentina Trapani,Tracey D. Bradshaw,A. D. Westwell,Malcolm F. G. Stevens +6 more
TL;DR: The most potent broad spectrum agent in the NCI cell panel was 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, unlike the 6-fluoro isomer (10d), produces no exportable metabolites in the presence of sensitive MCF-7 cells.
Journal ArticleDOI
The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate.
TL;DR: This review traces the development of a series of potent and selective antitumour benzothiazoles from the discovery of the initial lead compound, 2-(4-amino-3-methylphenyl)benzothiazole (DF 203) in 1995 to the identification of a clinical candidate, Phortress, scheduled to enter Phase 1 trials in Q1 2004.