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 i n this series, CJM 126, exhibits nanomolar in vitro activity against certai n human breast cancer cell lines. Structure-activity relationship studies w ithin 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 vitr o antitumour activity to ovarian, lung, renal and colon carcinoma cell line s with a remarkable selectivity profile (NCI analysis). Other interesting f eatures of this series include the highly unusual transient biphasic dose r esponse relationship and possible unique mechanism of action (NCI COMPARE a nalysis). 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203) has been selecte d as the lead compound in this series on the basis of superior in vivo resu lts.