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Molecular Pharmacology, Vol 6, 335-344, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Effect of 2,2' -(9,1O-Anthrylenedimethylene)bis(2-thiopseudourea) on Nucleic Acid Synthesis in Bacteria

PRISCILLA P. SAUNDERS 1 and GRADY F. SAUNDERS 1

1 From the Departments of Pathology and Developmental Therapeutics. The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77025

The mechanism of action of 2,2'-(9,10-anthrylenedimethylene)bis(2-thiopseudourea) (ATPU or pseudourea) has been investigated in bacterial systems. Inhibition of the growth of Bacillus subtilis by ATPU was reversed by the addition of nucleic acids. The synthesis of DNA and RNA in vivo was markedly inhibited by the drug. RNA synthesis in vitro catalyzed by purified DNA-dependent RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) of Bacillus stearothermophilus was sensitive to ATPU in a concentration-dependent manner. This inhibition was reversed by increasing the concentration of DNA primer. Evidence for a drug-DNA interaction was obtained from viscosity and cesium chloride buoyant density studies, which suggested the possible formation of intercalation complexes between DNA and ATPU.

Note:
ACKNOWLEDGMENTS The authors are indebted to Mrs. V. Liu, Miss G. Schultz, and Miss E. Fortin for excellent technical assistance. We thank Dr. E. Frei, III, for discussiouns on the clinical aspects of ATPU.

Submitted on February 24, 1970






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