RT Journal Article SR Electronic T1 Stimulation of Superoxide Formation by Actinomycin D and Its N2-Substituted Spin-Labeled Derivatives JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 432 OP 434 VO 17 IS 3 A1 BIRANDRA K. SINHA A1 MICHAEL G. Cox YR 1980 UL http://molpharm.aspetjournals.org/content/17/3/432.abstract AB The mechanism of action of actinomycin D (AMD) is related to its interactions with DNA and inhibition of RNA synthesis. Recently, it has been shown that AMD stimulates the formation of superoxide when incubated with microsomal proteins. We have prepared N2-[4-(2,2,6,6-tetramethyl-1-piperidinyloxyl)]actinomycin D and the related 1,3-diaminopropane analogs, which were found to be more active than AMD in vivo against P-388 leukemia cells in spite of their poor DNA binding properties. We have investigated the stimulation of superoxide formation by these compounds as a possible mechanism of action. These analogs are more effective in stimulating O2 uptake and the formation of O2- than the parent AMD. The better antitumor activities of these analogs may be related to the increased O2 formation in vivo. ACKNOWLEDGMENTS The authors wish to thank Drs. C. F. Chignell and R. P. Mason for their helpful discussions during the preparation of the manuscript.