Abstract
As part of a cooperative program carried out by the American pharmaceutical industry and the United States National Cancer Institute, a concerted effort was made to find unique cytotoxic antibiotics which inhibited macromolecule synthesis in, and growth of, cancer cells, to explore their potential as chemotherapeutic agents in the treatment of human malignant disease. During the course of this screening effort, the antibiotic, nogalamycin, an anthracyclinone produced by Streptomyces nogalater var. nogalater, was discovered because of its marked cytotoxicity against KB human epidermoid carcinoma cells growing in culture. Nogalamycin selectively inhibited the synthesis of ribonucleic acid (RNA) after binding to the deoxyribonucleic acid (DNA) template. Mammalian cells and bacteria in vitro and enzyme induction in rat liver all appeared to be inhibited by the same mechanism. When the antibiotic was found to inhibit the growth of several experimental animal tumors, it was considered for clinical trial as an anticancer agent, but unacceptable toxicity in animals precluded such investigations. The compound still provides an interesting tool to the biochemist for studying various aspects of the molecular mechanism of nucleic acid synthesis.
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References
Abrighi, F.E.: Nucleolar RNA synthetic activity in Chinese hamster cells in vitro and the effects of actinomycin D and nogalamycin. J. cell. Physiol. 69, 45–52 (1967).
Bhuyan, B.K., Dietz, A.: Fermentation, taxonomic, and biological studies of nogalamycin. Antimicrob. Ag. Chemother. 1965, 836–844 (1965).
Bhuyan, B.K., Kelly, KB., Smith, R.M.: Nogalamycin and its production. U.S. Patent 3, 183, 157 (May 11, 1965 ).
Bhuyan, B.K., Reusser, F.: Comparative biological activity of nogalamycin and its analogs. Cancer Ttes. 30, 984–989 (1970).
Bhuyan, B.K., Scheidt, L.G., Fraser, T.J.: Cell cycle phase specificity of antitumor agents. Cancer Res. 32, 398 - 407 (1972).
Bhuyan, B.K., Smith, C.G.: Differential interaction of nogalamycin with DNA of varying 631 base composition. Proc. nat. Acad. Sci. (Wash.) 54, 566–572 (1965).
Duprat, A.M., Miquel, M.T., Beetschen, J.C., Zalta, J.P.: Effect of chromomycin A3 and nogalamycin on urodelous amphibian embryo cells cultured in vitro; analogy with the effects of actinomycin D. C.R. Acad. Sci (Paris) D 265, 2080–2083 (1967).
Ellem, K.A.O., Rhode, S.L., III: Selective inhibition of ribosomal UNA synthesis in HeLa cells by nogalamycin, a dA:dT binding antibiotic. Biochim. biophys. Acta (Amst.) 209, 415–424 (1970).
Gray, G.D., Camiener, G.W., Bhuyan, B.K.: Nogalamycin effects in rat liver; inhibition of trytophan pyrrolase induction and nucleic acid biosynthesis. Cancer Res. 26, 2419–2424 (1966).
Jones, K.W.: The induction of paracrystalline thread-complexes in the nuclei of amphibian cells by actinomycin D and other DNA-binding antibiotics. J. Ultrastruc. Res. 18, 71–84 (1967).
Kersten, W., Kersten, H., Szybalski, W.: Physicochemical properties of complexes between deoxyribonucleic acid and antibiotics which affect ribonucleic acid synthesis (actinomycin, daunomycin, cinerubin, nogalamycin, chromomycin, mithramycin, and olivomycin). Bio-chemistry 5, 236–244 (1966).
Mauro, F., Madoc-Jones, H.: Age responses of cultured mammalian cells to cytotoxic drugs. Cancer Res. 30, 1397–1408 (1970).
Reich, E., Goldberg, I. H.: Actinomycin and nucleic acid function. Prog. nucleic Acid Res. molec. Biol. 8, 184–234 (1964).
Reusser, E., Bhuyan, B.K.: Comparative studies with three antibiotics binding to deoxyribonucleic acid. J. Bact. 94, 576–579 (1967).
Saunders, G.E., Reese, W.N., Saunders, P.P.: Differential reactivity of intercalative dyes with bacteriophage TP-84DNA. Biochim. biophys. Acta (Amst.) 190, 406–417 (1969).
Sentenac, A., Simon, E. J., Fromageot, P.: Initiation of chains by RNA polymerase and the effects of inhibitors studied by a direct filtration technique. Biochim. biophys. Acta (Amst.) 161, 299–308 (1968).
Simard, R., Bernhard, W.: Nucleolar segregation. Specific action of certain antimetabolites. Int. J. Cancer 1, 463 - 479 (1966).
Ward, D.C., Reich, E., Goldberg, I. H.: Base specificity in the interaction of polynucleotides with antibiotic drugs. Science 149, 1259–1263 (1965).
Waring, M.: Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs: evidence for intercalation. J. molec. Biol. 54, 247–279 (1970).
Wells, R.D., Larson, J. E.: Studies on the binding of actinomycin to DNA and DNA model polymers. J. molec. Biol. 49, 319–342 (1970).
Wiley, P.F.: Antibiotic nogalamycin iV-oxide. U.S. Patent 3, 449, 490 (June 10, 1969 ).
Wiley, P.F., Caron,E.L., Jr.: Antibiotic nogalarol, O-methylnogalarol, andnogalarene. U.S. Patent 3, 501, 569 (March 17, 1970 ).
Wiley, P. F., Mackellar, F.A., Caron, E.L., Kelly, R.B.: Isolation, characterization and 632 degradation of nogalamycin. Tetrahedron Let. 663–668 (1968).
Zeleznick, L.D., Sweeney, C.M.: Inhibition of deoxyribonuclease action by nogalamycin and U-12,241 by their interaction with DNA. Arch. Biochem. Biophys. 120, 292–295 (1967).
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Bhuyan, B.K., Smith, C.G. (1975). Nogalamycin. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65806-8_33
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DOI: https://doi.org/10.1007/978-3-642-65806-8_33
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