Phenazine-1-carboxamides: structure-cytotoxicity relationships for 9-substituents and changes in the H-bonding pattern of the cationic side chain.
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 IC(50)s between parent and P-glycoprotein expressing cell lines, suggesting that most of the compounds are not affected by the presence of this efflux pump.
Gamage
Swarna A
SA
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand. s.gamage@auckland.ac.nz
Rewcastle
Gordon W
GW
Baguley
Bruce C
BC
Charlton
Peter A
PA
Denny
William A
WA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002412:Cations; D010619:Phenazines; C420923:phenazine-1-carboxamide