NOVEL RIMINOPHENAZINE COMPOUNDS WITH IMPROVED ANTITUMOR PROPERTIES

The pro-oxidative and anti-proliferative activities of seven derivativ es of the prototype riminophenazine compound, clofazimine, have been i nvestigated in vitro. Unlike clofazimine, which has an isopropylimino group at the critical 2-position on the phenazine nucleus, the test ag ents are all cycloalkylimino compounds with varying numbers (3-12) of cyclical carbon atoms. Pro-oxidative activity was measured according t o the extent of superoxide generation by activated human neutrophils, while anti-proliferative effects were assayed using a human pharynx sq uamous carcinoma cell line. The pro-oxidative and especially the anti- proliferative activities of the test compounds were directly related t o the number of carbon atoms in the cycloalkylimino group. Maximal act ivity, more than double that of clofazimine, was observed with those c ompounds containing 5-8 cycloalkyl carbon atoms appear to enhance the anti-neoplastic potential of the riminophenazines.