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Molecular Pharmacology

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Research ArticleArticle

Miracil D: An Inhibitor of Ribonucleic Acid Synthesis in Bacillus subtilis

I. BERNARD WEINSTEIN, ROBIN CHERNOFF, IRENE FINKELSTEIN and ERICH HIRSCHBERG
Molecular Pharmacology November 1965, 1 (3) 297-305;
I. BERNARD WEINSTEIN
Departments of Medicine and Biochemistry, Columbia University College of Physicians and Surgeons, and Department of Medicine, Francis Delafield Hospital, New York, New York
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ROBIN CHERNOFF
Departments of Medicine and Biochemistry, Columbia University College of Physicians and Surgeons, and Department of Medicine, Francis Delafield Hospital, New York, New York
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IRENE FINKELSTEIN
Departments of Medicine and Biochemistry, Columbia University College of Physicians and Surgeons, and Department of Medicine, Francis Delafield Hospital, New York, New York
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ERICH HIRSCHBERG
Departments of Medicine and Biochemistry, Columbia University College of Physicians and Surgeons, and Department of Medicine, Francis Delafield Hospital, New York, New York
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Abstract

Miracil D (1-diethylaminoethylamino-4-methyl-10-thiaxanthenone) is effective against schistosomiasis in man and against experimental tumors in mice, but its mode of action had not been defined. The present study indicates that at 20 µg/ml the drug arrests the growth of Bacillus subtilis. This antibacterial action is also exhibited by a tumor-inhibitory derivative, but not by a derivative devoid of carcinostatic activity. Incubation of B. subtilis with 14C-uracil, thymidine, or leucine in the presence of 20 µg/ml of Miracil D indicated a complete inhibition of RNA synthesis, immediate but less severe inhibition of protein synthesis, and no inhibition of DNA synthesis. The drug has absorption maxima at 442 and 330 mµ. In the presence of native DNA there is quenching of absorption at these wavelengths, with a shift in the maxima to 450 and 337 mµ. In heat-denaturation studies, Miracil D raised the Tm of DNA by 15°. Similar studies gave evidence for a lesser affinity between Miracil D and sRNA. These results indicate that the major action of this drug in B. subtilis is to complex with DNA, thereby blocking DNA-dependent RNA synthesis.

ACKNOWLEDGMENT This work was supported in part by U.S. Public Health Service research grant (R10 CA 02332) and training grant (T4 CA 5011) from the National Cancer Institute. One of us (I.B.W.) is a Career Scientist of the New York City Health Research Council (I-190).

  • Copyright ©, 1965, by Academic Press Inc.

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Molecular Pharmacology
Vol. 1, Issue 3
1 Nov 1965
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Research ArticleArticle

Miracil D: An Inhibitor of Ribonucleic Acid Synthesis in Bacillus subtilis

I. BERNARD WEINSTEIN, ROBIN CHERNOFF, IRENE FINKELSTEIN and ERICH HIRSCHBERG
Molecular Pharmacology November 1, 1965, 1 (3) 297-305;

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Research ArticleArticle

Miracil D: An Inhibitor of Ribonucleic Acid Synthesis in Bacillus subtilis

I. BERNARD WEINSTEIN, ROBIN CHERNOFF, IRENE FINKELSTEIN and ERICH HIRSCHBERG
Molecular Pharmacology November 1, 1965, 1 (3) 297-305;
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