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Structure activity relationships for tricyclic‐carboxamide topoisomerase II poisons indicate that cytotoxicity is enhanced by the presence of methyl, and other, groups in the position peri to the carboxamide. Linked dimers of phenazine‐1‐carboxamides are potent cytotoxins and one phenazine dimer, MLN944 (alternatively XR5944), has been in clinical trial. MLN944 is a template inhibitor of transcription,...
MLN 944 is a bisintercalating DNA‐binding antitumor agent known to be a template inhibitor of transcription. Previous 1H NMR studies of its d(ATGCAT)2 complex concluded that its phenazine chromophores are protonated. However, we find that this is not so, which has important consequences for the charged state of the ligand, for the orientation of its 1‐carboxamide group in the complex, and for the...
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