It is proposed to synthesize and test biologically an analog of actinomycin with a phenazine skeleton instead of a 4,9-dimethyl-2- aminophenoxazinone-3. The compound will be tested for binding to DNA, for inhibition of RNA synthesis and for antitumor activity. Its activity with a chemotherapeutic index, possibly improved over that of actinomycin, is expected because of the intercalative binding properties of phenazine antibiotics and because of the relative unimportance for activity of the peripheral groups - other than the two polypeptides - in actinomycin itself. The synthesis will proceed via phenazine-1,9- dicarboxylic acid to which first 2 molecules L-Thr and then two molecules of the tetrapeptide D-Val-L-Pro-Sar-L-N-MeVal will be coupled, followed by lactonization of the twin pentapeptides.
NIH ExPorter
NIH ExPorter