| Abstract
| - A new series of 2-(4-aminophenyl)benzothiazoles substitutedin the phenyl ring and benzothiazole moiety has been synthesized by simple, high-yielding routes.The parent molecule 5ashows potent inhibitory activity in vitro in the nanomolarrange against a panel of humanbreast cancer cell lines, but is inactive (IC50> 30 μM)against other cell types: activity againstthe sensitive breast lines MCF-7 and MDA 468 is characterized by abiphasic dose−responserelationship. Structure−activity relationships derived usingthese cell types has revealed thatactivity follows the heterocyclic sequence benzothiazole > benzoxazole≫ benzimidazole andthat 2-(4-aminophenyl)benzothiazoles bearing a 3‘-methyl-9a, 3‘-bromo- 9c, 3‘- iodo- 9f,and3‘-chloro-substituent 9i are especially potent and theiractivity extends to ovarian, lung, andrenal cell lines. Four compounds have been evaluated invivo against human mammarycarcinoma models in nude mice. Compound 9a showed themost potent growth inhibitionagainst the ER+ (MCF-7 and BO) and ER-(MT-1 and MT-3) tumors. Our efforts to identifya pharmacological mechanism of action for these intriguing compoundshave not, as yet, beensuccessful.
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