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Applied Microbiology and Biotechnology May 2019Rebeccamycin is an antibiotic and antitumor substance isolated from the filamentous bacterium Lentzea aerocolonigenes. After its discovery, investigations of... (Review)
Review
Rebeccamycin is an antibiotic and antitumor substance isolated from the filamentous bacterium Lentzea aerocolonigenes. After its discovery, investigations of rebeccamycin focused on elucidating its structure, biological activity, and biosynthetic pathway. For potential medical application, a sufficient drug supply has to be ensured, meaning that the production process of rebeccamycin plays a major role. In addition to the natural production of rebeccamycin in L. aerocolonigenes, where the complex cell morphology is an important factor for a sufficient production, rebeccamycin can also be heterologously produced or chemically synthesized. Each of these production processes has its own challenges, and first approaches to production often lead to low final product concentrations, which is why process optimizations are performed. This review provides an overview of the production of rebeccamycin and the different approaches used for rebeccamycin formation including process optimizations.
Topics: Antibiotics, Antineoplastic; Bacteria; Carbazoles; Industrial Microbiology
PubMed: 30888461
DOI: 10.1007/s00253-019-09741-y -
The Journal of Organic Chemistry Aug 2016The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available...
The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-β-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.
Topics: Aldehydes; Antibiotics, Antineoplastic; Furans; Magnetic Resonance Spectroscopy; Molecular Structure; Polyketides; Quinolizines; Stereoisomerism; Sulfur Compounds
PubMed: 27347696
DOI: 10.1021/acs.joc.6b01255 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2015The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by...
The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2-deoxy β-C-arylglycoside, and a late-stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2-deoxy sugar subunits for structure and activity relationship studies.
Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Deoxy Sugars; Glycosylation; Guanidines; Molecular Structure; Oligosaccharides; Stereoisomerism
PubMed: 26250826
DOI: 10.1002/chem.201502113 -
Advances in Protein Chemistry and... 2017Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations... (Review)
Review
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease. Ascochlorin (ASC), an isoprenoid antibiotic isolated initially from the fermented broth of Ascochyta viciae, and its synthetic derivatives have recently demonstrated substantial antineoplastic effects in a variety of tumor cell lines and mouse models. The major focus of this review article is to briefly analyze the chemopreventive as well as therapeutic properties of ASC and its derivatives and to identify the multiple molecular targets modulated by this novel class of anticancer agent.
Topics: Alkenes; Animals; Antibiotics, Antineoplastic; Apoptosis; Ascomycota; Autophagy; Humans; Neoplasm Invasiveness; Neoplasms; Phenols
PubMed: 28427561
DOI: 10.1016/bs.apcsb.2017.01.001 -
Cancer Clinical Trials 1981Acivicin [(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; AT-125; NSC-163501] is a fermentation product of Streptomyces sviceus which is active in... (Review)
Review
Acivicin [(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; AT-125; NSC-163501] is a fermentation product of Streptomyces sviceus which is active in a variety of mouse tumor models including the L1210 and P388 leukemias, the M5076 ovarian carcinoma, and the MX-1 human breast tumor xenograft. Antitumor activity is probably mediated through the inhibition of enzymes catalyzing amido transfer from L-glutamine, especially CTP synthetase and XMP aminase. In mice, acivicin is absorbed systemically via the p.o., I.P., and S.C. routes and is predominantly excreted in the urine in unchanged form. Although a wide variety of toxicities, including myelosuppression, were noted in dogs and monkeys, vomiting, diarrhea, and pathologic lesions of the GI tract predominated in both species. A marked cumulative toxicity was noted in dogs with 16 mg/m2/day being the lethal dose on the daily x 5 schedule compared to 1000 mg/m2 on the single-dose schedule. An interesting phenomenon was noted in mice wherein older male mice were more resistant to the toxic effects of the drug than female or younger male mice. This sex and age difference in susceptibility to acivicin toxicity was shown to be correlated with differences in pharmacokinetics; older male mice cleared acivicin at approximately twice the rate of females or younger males. No sex differences in toxicity were noted in dogs or monkeys. Because of its activity in mouse tumor systems and acceptable preclinical toxicology patterns, the drug is being introduced into clinical phase I studies under the sponsorship of the National Cancer Institute.
Topics: Animals; Antibiotics, Antineoplastic; Glycine; Humans; Isoxazoles; Neoplasms; Neoplasms, Experimental; Oxazoles
PubMed: 7026076
DOI: No ID Found -
Anti-cancer Agents in Medicinal... Feb 2008The enediyne antibiotics, the potent anticancer agents that contain diyne-ene functional groups, are appreciated for their novel molecular architecture, their remarkable... (Review)
Review
The enediyne antibiotics, the potent anticancer agents that contain diyne-ene functional groups, are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mechanism of action. Their anticancer activity is apparently due to their ability to damage DNA through radical-mediated hydrogen abstraction. The enediyne antibiotics show markedly cytotoxicities against cancers in vitro and in vivo. Lidamycin is a member of the enediyne anticancer antibiotic family. This review examines lidamycin with particular emphasis on the discovery, the biological properties and its structure-activity relationships. In addition, the possible mechanisms of action of lidamycin are described. Recent progress, particularly in the areas of biosynthesis, and immunoconjugates are highlighted. Finally, the pharmacological applications of lidamycin in cancer therapy and its potential use as anticancer agents are also discussed.
Topics: Aminoglycosides; Animals; Antibiotics, Antineoplastic; Cell Proliferation; DNA Damage; DNA, Neoplasm; Enediynes; Humans; Molecular Conformation; Neoplasms; Structure-Activity Relationship
PubMed: 18288918
DOI: 10.2174/187152008783497055 -
Current Topics in Medicinal Chemistry 2008The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and... (Review)
Review
The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures' means to biosynthesize such complex, exotic molecules. Presented here is a review of the current progress in delineating the biosynthesis of the enediynes with an emphasis on the model enediyne, C-1027.
Topics: Actinobacteria; Antibiotics, Antineoplastic; Enediynes; Multigene Family; Polyketide Synthases
PubMed: 18397168
DOI: 10.2174/156802608783955656 -
The Journal of Antibiotics Apr 1992
Topics: Actinomyces; Antibiotics, Antineoplastic; Drug Screening Assays, Antitumor; Gram-Positive Bacteria; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Naphthoquinones; Stereoisomerism; Tumor Cells, Cultured
PubMed: 1592691
DOI: 10.7164/antibiotics.45.584 -
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 -
The Journal of Antibiotics Dec 1969
Topics: Animals; Antibiotics, Antineoplastic; Carcinoma 256, Walker; Chromatography, Paper; Chromatography, Thin Layer; Infrared Rays; Leukemia, Experimental; Mice; Microbial Sensitivity Tests; Rats; Spectrum Analysis; Streptomyces; Ultraviolet Rays
PubMed: 5367394
DOI: 10.7164/antibiotics.22.608