PT  - JOURNAL ARTICLE
AU  - BIRANDRA K. SINHA
AU  - MICHAEL G. Cox
TI  - Stimulation of Superoxide Formation by Actinomycin D and Its N<sup>2</sup>-Substituted Spin-Labeled Derivatives
DP  - 1980 May 01
TA  - Molecular Pharmacology
PG  - 432--434
VI  - 17
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/17/3/432.short
4100  - http://molpharm.aspetjournals.org/content/17/3/432.full
SO  - Mol Pharmacol1980 May 01; 17
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.