Antitumor Antibiotics

Oki, Taikan; Yoshimoto, Akihiro

doi:10.1016/b978-0-12-040303-5.50014-9

Cited by 4 publications

(3 citation statements)

References 98 publications

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“…. produced by Streptomyces peucetius, daunomycin and adria- plastic activity (Marshall et al 1977;Strauss 1978;Oki and Yoshimoto 1979;Remers 1979;McGuire et al 1980).…”

Section: Introductionmentioning

confidence: 99%

Nutrient effects on anthracycline production by Streptomyces peucetius in a defined medium

Dekleva¹,

Titus²,

Strohl³

1985

Can. J. Microbiol.

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A defined medium was developed for Streptomyces peucetius that optimally contained 0.5 mM magnesium, 1 mM phosphate, 75-125 mM glucose, 10 mM nitrate, and microelements. Poorer results were obtained with nitrite, aspartate, or ammonia as sole nitrogen sources. Other carbon sources which supported best growth and highest anthracycline titers were fructose, maltose, and soluble starch. In each case, substantial residual carbon remained at the end of 6 days, suggesting a lack of catabolite repression by the carbohydrate carbon sources on anthracycline biosynthesis. Studies involving limiting and nonlimiting concentrations of glucose supplemented with arabinose, a poorly utilizable carbon source, indicated that high carbon concentrations were not necessary for osmotic stabilization. Inorganic phosphate was found to have an inhibitory effect on anthracycline production. Furthermore, when cultures at early stages of anthracycline production were spiked with inorganic phosphate, a delay in further anthracycline production resulted until the added phosphate was depleted. A 10% inoculum of stationary phase cells yielded the best growth and most consistent anthracycline production. Spectrophotometric analyses at 495 nm of chloroform--methanol-extracted material were also found to be useful for the determination of total anthracyclines in culture extracts.

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“…. produced by Streptomyces peucetius, daunomycin and adria- plastic activity (Marshall et al 1977;Strauss 1978;Oki and Yoshimoto 1979;Remers 1979;McGuire et al 1980).…”

Section: Introductionmentioning

confidence: 99%

Nutrient effects on anthracycline production by Streptomyces peucetius in a defined medium

Dekleva¹,

Titus²,

Strohl³

1985

Can. J. Microbiol.

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“…The drug cytarabine (Cytostar) for non-Hodgkin's lymphoma was originally isolated from a sponge (12). Most of the important antitumor compounds used for chemotherapy of tumors are microbially produced antibiotics (94,95). These include actinomycin D, mitomycin, bleomycins, and the anthracyclines daunorubicin and doxorubicin.…”

Section: Anticancer Drugsmentioning

confidence: 99%

Natural Products and Drug Discovery

Demain

Zhang

Natural Products

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SummaryFor more than 50 yr, natural products have served us well in combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites helped to double our life span, reduced pain and suffering, and revolutionized medicine. The increased development of resistance to older antibacterial, antifungal, and antitumor drugs has been challenged by (1) newly discovered antibiotics (e.g., candins, epothilones); (2) new semisynthetic versions of old antibiotics (e.g., ketolides, glycylcyclines); (3) older underutilized antibiotics (e.g., teicoplainin); and (4) new derivatives of previously undeveloped narrow-spectrum antibiotics (e.g., streptogramins). In addition, many antibiotics are used commercially, or are potentially useful in medicine for purposes other than their antimicrobial action. They are used as antitumor agents, enzyme inhibitors including powerful hypocholesterolemic agents, immunosuppressive agents, antimigraine agents, and so on. A number of these products were first discovered as antibiotics that failed in their development as such, or as mycotoxins.It is unfortunate that the pharmaceutical industry has downgraded natural products just at the time that new assays are available and major improvements have been made in detection, characterization, and purification of small molecules. With the advent of combinatorial biosynthesis, thousands of new des4oeatives can now be made by a biological technique complementary to combinatorial chemistry. Furthermore, only a minor proportion of bacteria and fungi, i.e., 0.1-5%, have thus far been examined for secondary metabolite production. New methods are being developed to cultivate the so-called unculturable microbes from the soil and the sea. High-throughput screening (HTS) of combinatorial chemicals has not provided the numbers of high-quality leads that were anticipated. It has virtually eliminated the most unique source of chemical diversity, i.e., natural products, from the playing field, in favor of combinatorial chemistry. Combinatorial chemistry mainly yields minor modifications of present-day drugs and absolutely requires new scaffolds on which to build. Although comparative genomics is capable of disclosing new targets for drugs, the number of targets is so large that it requires tremendous investments of time and money to set up all the screens necessary to exploit this resource. This can be handled only by HTS methodology, which demands libraries of millions of chemical entities. Although such targets would be excellent for screening natural products, the industry has failed to exploit this unique opportunity and has opted to save funds by eliminating natural-product departments or decreasing their relevance in the hunt for new drugs. It is clear that the future success of the pharmaceutical industry depends on the combining of complementary technologies such as natural product discovery, HTS, integrative and systems biology, combinatorial biosynthesis, and combinatorial chemistry.

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“…The biochemical and medical aspects of these compounds have been covered in several excellent reviews (1)(2)(3)(4)(5)(6). The most important aspects of structure and activity relationships between the different anthracyclines will be summarized here and, along with more recent information, the increasing importance of the 11-deoxy anthracyclines related to aclacinomycin will be shown.…”

mentioning

confidence: 99%

Studies in anthracycline synthesis

Crowley

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Antitumor Antibiotics

Cited by 4 publications

References 98 publications

Nutrient effects on anthracycline production by Streptomyces peucetius in a defined medium

Nutrient effects on anthracycline production by Streptomyces peucetius in a defined medium

Natural Products and Drug Discovery

Studies in anthracycline synthesis

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