Synthesis and antitumour evaluation of novel 2- phenylbenzimidazoles

Kadri, Hachemi, Matthews, Charles S., Bradshaw, Tracey D., Stevens, Malcolm F. G. and Westwell, Andrew D. (2008) Synthesis and antitumour evaluation of novel 2- phenylbenzimidazoles. Journal of Enzyme Inhibition and Medicinal Chemistry, 23(5), pp. 641-647. ISSN (print) 1475-6366


A new series of fluorinated and non-fluorinated 2-phenylbenzimidazoles bearing oxygenated substituents on the phenyl ring has been synthesized. Synthesis of the new series was based on our previous discovery of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610) as a potent and selective antitumour agent in vitro (sub-nanomolar GI(50) in sensitive human cancer cell lines), but with poor aqueous solubility and lack of a definitive cellular target limiting further development. In this study we test the hypothesis that 2-phenylbenzimidazoles with similar substitution patterns to PMX 610 would retain potent antitumour activity but with potentially superior pharmaceutical properties. In general the new compounds were less active than the former benzothiazole series in vitro when tested against the breast cancer cell lines MCF-7 and MDA 468; however the two most active compounds in the present series (3j and 3k) exhibit low micromolar GI(50) values in both cell lines and provide the opportunity for further chemical derivatization with a view to target identification.

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