The discovery of the potent and selective antitumour agent 2-(4-amino-3-methylphenyl)benzothiazole (DF 203) and related compounds.
The development of a series of potent and selective antitumour agents, the 2-(4-aminophenyl)benzothiazoles, is described. The original lead compound in this series, CJM 126, exhibits nanomolar in vitro activity against certain human breast cancer cell lines. Structure-activity relationship studies within this simple antitumour benzothiazole pharmacophore revealed that 2-(4-aminophenyl) benzothiazoles bearing a 3'- methyl, 3'-bromo, 3'-iodo or 3'-chloro substituent are especially potent, extending the spectrum of in vitro antitumour activity to ovarian, lung, renal and colon carcinoma cell lines with a remarkable selectivity profile (NCI analysis). Other interesting features of this series include the highly unusual transient biphasic dose response relationship and possible unique mechanism of action (NCI COMPARE analysis). 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203) has been selected as the lead compound in this series on the basis of superior in vivo results
Bradshaw
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Cancer Research Laboratories, School of Pharmaceutical Sciences, University of Nottingham, University Park, UK. Andrew.Westwell@nottingham.ac.uk
Stevens
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Westwell
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D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles; D006801:Humans; D011355:Prodrugs; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C111133:2-(4-aminophenyl)benzothiazole; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D052160:Benzothiazoles; C122062:NSC 674495; D011355:Prodrugs; D013844:Thiazoles