Phenazine-1-carboxamides: Structure–cytotoxicity relationships for 9-substituents and changes in the H-bonding pattern of the cationic side chain Original Research Article

A series of phenazine-1-carboxamides were prepared, including variations in both chromophore substituents and the nature of the cationic side chain. The novel side-chain analogues were prepared from the corresponding phenazine-1-carboxylic acids via Schmidt conversion to the 1-amines and from the corresponding 1-halides. Structure–cytotoxicity relationships for these compounds in a panel of tumor cell lines showed that there is very limited scope for variation of the structure of the 1-carboxamide side chain, consistent with the recent structural model of how tricyclic carboxamides bind to DNA. There was generally little difference in IC50s between parent and P-glycoprotein expressing cell lines, suggesting that most of the compounds are not affected by the presence of this efflux pump.