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Proceedings of the National Academy of... May 1990Dynemicin is a hybrid containing anthraquinone and enediyne cores, which contribute to binding and cleavage of DNA, respectively. DNA strand scission by the antitumor...
Dynemicin is a hybrid containing anthraquinone and enediyne cores, which contribute to binding and cleavage of DNA, respectively. DNA strand scission by the antitumor antibiotic is significantly enhanced by the addition of NADPH or thiol compounds. The preferential cutting site of dynemicin is on the 3' side of purine bases (i.e., 5'-GC, -GT, and -AG) and is clearly different from the cutting sites of esperamicin and calicheamicin. The double-stranded and the stem regions of single-stranded DNAs are preferentially cleaved by dynemicin. Therefore, dynemicin may be a useful reagent for probing secondary structures of DNA. Pretreatment of DNA with Adriamycin and actinomycin D alters the cutting mode of dynemicin. Dynemicin-mediated DNA breakage is strongly inhibited by pretreatment of the DNA with distamycin A and anthramycin, suggesting that dynemicin interacts with the minor groove of the DNA helix. Intercalation of the anthraquinone core into the DNA followed by the attack of the phenyl diradical formed from the enediyne core is considered as a possible mechanism of action of dynemicin.
Topics: Anthraquinones; Antibiotics, Antineoplastic; Base Sequence; DNA; Enediynes; Molecular Sequence Data; Nucleic Acid Conformation; Plasmids; Restriction Mapping
PubMed: 2339123
DOI: 10.1073/pnas.87.10.3831 -
The Journal of Antibiotics Dec 1985A new antitumor antibiotic, terpentecin was isolated from the culture broth of strain MF730-N6. Strain MF730-N6, isolated from soil, was found to belong to the genus...
A new antitumor antibiotic, terpentecin was isolated from the culture broth of strain MF730-N6. Strain MF730-N6, isolated from soil, was found to belong to the genus Kitasatosporia. The antibiotic was extracted with chloroform, purified by column chromatography using silica gel and Diaion HP-20 successively, and finally purified by high performance reverse-phase thin layer chromatography. The molecular formula of terpentecin was determined to be C20H28O6 (molecular weight, 364). The antibiotic inhibited the growth of Gram-positive and Gram-negative bacteria, and prolonged the survival period of mice bearing leukemia L-1210, P388 and Ehrlich ascites carcinoma.
Topics: Actinomycetales; Animals; Antibiotics, Antineoplastic; Bacteria; Chemical Phenomena; Chemistry; Diterpenes; Fermentation; Mice; Neoplasms, Experimental
PubMed: 3841535
DOI: 10.7164/antibiotics.38.1664 -
Journal of Molecular Biology Oct 2013Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential...
Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3.1-Å crystal structure of de-6-MSA-pactamycin bound to its target site on the Thermus thermophilus 30S ribosomal subunit. Although de-6-MSA-pactamycin lacks the MSA moiety, it shares the same binding site as pactamycin and induces a displacement of nucleic acid template bound at the E-site of the 30S. The structure highlights unique interactions between this pactamycin analog and the ribosome, which paves the way for therapeutic development of related compounds.
Topics: Antibiotics, Antineoplastic; Crystallography, X-Ray; Models, Molecular; Molecular Conformation; Pactamycin; Protein Binding; RNA, Ribosomal, 16S; Ribosome Subunits, Small, Bacterial; Thermus thermophilus
PubMed: 23702293
DOI: 10.1016/j.jmb.2013.05.004 -
The Journal of Antibiotics Apr 1994The biosynthesis of antitumor antibiotic cytogenin, 3-hydroxymethyl-6-methoxy-8-hydroxy-isocoumarin, was studied by feeding 14C- or 13C-labeled compounds to culture of...
The biosynthesis of antitumor antibiotic cytogenin, 3-hydroxymethyl-6-methoxy-8-hydroxy-isocoumarin, was studied by feeding 14C- or 13C-labeled compounds to culture of the producing organism, Streptoverticillium eurocidicum MI43-37F11. 14C-Acetate and 14C-methionine were efficiently incorporated into cytogenin as precursors. 13C NMR studies proved that the carbon skeleton of cytogenin is derived from pentaketide intermediate due to head-to-tail condensation of five acetate units and methyl group of 6-OCH3 is derived from methionine. It was suggested that 3-hydroxymethyl and/or 6-methoxy group of cytogenin were metabolized by hydroxylation and/or methylation from three intermediates.
Topics: Acetates; Antibiotics, Antineoplastic; Chromatography, High Pressure Liquid; Coumarins; Culture Media; Hydroxylation; Isocoumarins; Magnetic Resonance Spectroscopy; Methionine; Methylation; Prodrugs; Spectrophotometry, Ultraviolet; Streptomycetaceae
PubMed: 8195044
DOI: 10.7164/antibiotics.47.440 -
Antimicrobial Agents and Chemotherapy Mar 1974All amino groups in a proteinous antitumor antibiotic, neocarzinostatin, were reacted with succinic anhydride yielding bis-N-succinyl neocarzinostatin which retained...
All amino groups in a proteinous antitumor antibiotic, neocarzinostatin, were reacted with succinic anhydride yielding bis-N-succinyl neocarzinostatin which retained biological activity in vitro against human cell lines and a bacterium. Amino groups in neocarzinostatin do not appear to play an important role in the activity.
Topics: Antibiotics, Antineoplastic; Proteins; Sarcina; Succinates
PubMed: 4840443
DOI: 10.1128/AAC.5.3.354 -
The Journal of Antibiotics Oct 1976The antitumor protein actinoxanthin exhibits high inhibitory activity against a number of gram-positive bacteria and some strains of transplantable leucoses and related...
The antitumor protein actinoxanthin exhibits high inhibitory activity against a number of gram-positive bacteria and some strains of transplantable leucoses and related tumors. Actinoxanthin was shown to consist of a single polypeptide chain crosslinked by two disulfide bonds and to contain 107 amino acid residues. Reduced and alkylated actinoxanthin was digested with chymotrypsin, thermolysin and trypsin. Based on the sequence analysis of fragments so obtained the complete amino acid sequence and the location of disulfide bonds of actinoxanthin has been proposed. The high degree homology of some regions of actinoxanthin and the antitumor protein neocarzinostatin have been revealed.
Topics: Alkylation; Amino Acid Sequence; Antibiotics, Antineoplastic; Chemical Phenomena; Chemistry; Oxidation-Reduction; Peptide Chain Termination, Translational; Peptides
PubMed: 994323
DOI: 10.7164/antibiotics.29.1026 -
The Journal of Antibiotics Sep 1982An actinomycete, isolated from a soil sample from Ontario, Canada, was studied taxonomically and named Actinosporangium bohemicum sp. nov. strain C-36,145. This strain...
An actinomycete, isolated from a soil sample from Ontario, Canada, was studied taxonomically and named Actinosporangium bohemicum sp. nov. strain C-36,145. This strain was found to produce a complex mixture of e-pyrromycinone glycosides having antitumor properties. Marcellomycin, a member of this complex, was selected for further study. Conditions for production of this antibiotic were developed in flask studies and scaled-up to the 3,000-liter fermentor stage.
Topics: Actinomycetales; Animals; Anthracyclines; Antibiotics, Antineoplastic; Cell Wall; Culture Media; Escherichia coli; Fermentation; Leukemia P388; Mice; Naphthacenes
PubMed: 6754675
DOI: 10.7164/antibiotics.35.1174 -
The Journal of Antibiotics Aug 1992Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and potent...
Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and potent in vivo antitumor activity against P388 and L1210 leukemias, and B16 melanoma. Sultriecin is composed of several unique structural units; a conjugated triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality.
Topics: Animals; Antibiotics, Antineoplastic; Antifungal Agents; Humans; Lactones; Mice; Neoplasms, Experimental; Pyrones; Streptomyces
PubMed: 1399844
DOI: 10.7164/antibiotics.45.1239 -
Mitochondrion Mar 2019Doxorubicin (DOX) is a highly effective anthracycline antibiotic. Unfortunately, the clinical use of DOX is limited by the risk of deleterious effects to cardiac and...
Doxorubicin (DOX) is a highly effective anthracycline antibiotic. Unfortunately, the clinical use of DOX is limited by the risk of deleterious effects to cardiac and respiratory (i.e. diaphragm) muscle, resulting from mitochondrial reactive oxygen species (ROS) production. In this regard, exercise is demonstrated to protect against DOX-induced myotoxicity and prevent mitochondrial dysfunction. However, the protective mechanisms are currently unclear. We hypothesized that exercise may induce protection by increasing the expression of mitochondria-specific ATP-binding cassette (ABC) transporters and reducing mitochondrial DOX accumulation. Our results confirm this finding and demonstrate that two weeks of exercise preconditioning is sufficient to prevent cardiorespiratory dysfunction.
Topics: Animals; Antibiotics, Antineoplastic; Diaphragm; Doxorubicin; Female; Mitochondria; Myocardium; Physical Conditioning, Animal; Rats, Sprague-Dawley
PubMed: 29474837
DOI: 10.1016/j.mito.2018.02.005 -
The Journal of Antibiotics Apr 1979The antifungal antibiotic, prumycin, was studied for antitumor activity against several tumor systems. It was found to possess potential antitumor activity against a...
The antifungal antibiotic, prumycin, was studied for antitumor activity against several tumor systems. It was found to possess potential antitumor activity against a well-established mouse mammary adenocarcinoma in C3H/He mice. It was also active in prolongation of the lifespan of mice bearing P-388 lymphocytic leukemia. Moreover, prumycin did not depress the white blood cell counts in the mouse peripheral blood. However, severe alopecia was observed in mice treated with this agent at dosage level near the LD50.
Topics: Aminoglycosides; Animals; Antibiotics, Antineoplastic; Female; Lethal Dose 50; Leukemia, Experimental; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Methylcholanthrene; Mice; Neoplasms, Experimental; Sarcoma 180; Sarcoma, Experimental; Sarcoma, Yoshida; Time Factors
PubMed: 468722
DOI: 10.7164/antibiotics.32.347