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The Journal of Antibiotics Nov 1974
Topics: Acetylation; Actinomycetales; Amino Sugars; Aminoglycosides; Antibiotics, Antineoplastic; Chemical Phenomena; Chemistry; Ethers; Hydrogenation; Hydrolysis; Methylation
PubMed: 4452659
DOI: 10.7164/antibiotics.27.866 -
Cancer Letters Sep 2020The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and...
The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and metastatic PCa treatment. However, the occurrence of aberrant expression, mutated or splice variants of AR confers resistance to androgen ablation therapy (ADT), radiotherapy or chemotherapy in AR-positive PCa. Therapeutic strategies that effectively inhibit the expression and/or transcriptional activity of full-length AR, mutated AR and AR splice variants have remained elusive. In this study, we report that mithramycin (MTM), an antineoplastic antibiotic, suppresses cell proliferation and exhibits dual inhibitory effects on expression and transcriptional activity of AR and AR splice variants. MTM blocks AR recruitment to its genomic targets by occupying AR enhancers and causes downregulation of AR target genes, which includes key DNA repair factors in DNA damage repair (DDR). We show that MTM significantly impairs DDR and enhances the effectiveness of ionizing radiation or the radiomimetic agent Bleomycin in PCa. Thus, the combination of MTM treatment with RT or radiomimetic agents, such as bleomycin, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.
Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; DNA Damage; DNA Repair; Humans; Male; Plicamycin; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 32485222
DOI: 10.1016/j.canlet.2020.05.027 -
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 -
The Journal of Antibiotics Mar 2015As part of an ongoing project to explore filamentous fungi for anticancer and antibiotic leads, 11 compounds were isolated and identified from an organic extract of the...
As part of an ongoing project to explore filamentous fungi for anticancer and antibiotic leads, 11 compounds were isolated and identified from an organic extract of the fungus Scytalidium album (MSX51631) using bioactivity-directed fractionation against human cancer cell lines. Of these, eight compounds were a series of sorbicillinoid analogs (1-8), of which four were new (scalbucillin A (2), scalbucillin B (3), scalbucillin C (6) and scalbucillin D (8)), two were phthalides (9-10) and one was naphthalenone (11). Compounds (1-11) were tested in the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compound 1 was the most potent with IC50 values of 1.5 and 0.5 μM, followed by compound 5 with IC50 values of 2.3 and 2.5 μM at 72 h. Compound 1 showed a 48-h IC50 value of 3.1 μM when tested against the lymphocytic leukemia cell line OSU-CLL, while the nearly identical compound 5 had almost no activity in this assay. Compounds 1 and 5 showed selective and equipotent activity against Aspergillus niger with minimum IC values of 0.05 and 0.04 μg ml(-1) (0.20 and 0.16 μM), respectively. The in vitro hemolytic activity against sheep erythrocytes of compounds 1 and 5 was investigated and were found to provoke 10% hemolysis at 52.5 and 45.0 μg ml(-1), respectively, indicative of a promising safety factor.
Topics: Antibiotics, Antineoplastic; Antifungal Agents; Aspergillus; Cell Line, Tumor; Hemolysis; Humans; Magnetic Resonance Spectroscopy; Mitosporic Fungi; Structure-Activity Relationship
PubMed: 25248727
DOI: 10.1038/ja.2014.125 -
Medical Science Monitor : International... 2000Anthracycline antibiotics are widely used antineoplastic agents and their efficacy for the treatment of various haemopoietic or solid tumours has been well established... (Review)
Review
Anthracycline antibiotics are widely used antineoplastic agents and their efficacy for the treatment of various haemopoietic or solid tumours has been well established in clinical practice. Cardiotoxicity is one of the most serious side effects of anthracyclines. The risk of cumulative, life-threatening toxic cardiomyopathy limits their therapeutic potential. In this article, acute, subacute, chronic and late-onset cardiac function impairment associated with anthracycline administration has been characterised. The current views on the methods of detection, pathogenesis and prevention of such toxicity have been reviewed.
Topics: Acute Disease; Antibiotics, Antineoplastic; Cardiomyopathies; Chronic Disease; Heart; Humans; Risk Factors; Time Factors
PubMed: 11208348
DOI: No ID Found -
The Journal of Biological Chemistry May 1978Macromomycin is a protein isolated from the culture filtrate of Streptomyces macromomyceticus. It is an antibiotic and also cytotoxic to a broad spectrum of carcinoma...
Macromomycin is a protein isolated from the culture filtrate of Streptomyces macromomyceticus. It is an antibiotic and also cytotoxic to a broad spectrum of carcinoma cells, the ID50 for P388 leukemia cells being 1 X 10(-9) M. Macromomycin binds rapidly and tightly to the P388 cell membrane and the eventual death of the cell cannot be reversed by either washing the toxin away or treating the cell with trypsin. The cytotoxicity does not appear to be specific for any phase of the P388 cell cycle. Macromomycin is a single polypeptide, pI 5.38, devoid of methionine and arginine residues and contains 4 cysteine residues joined by two intramolecular disulfide bonds. The cytotoxicity results in inhibition of DNA, RNA, and protein synthesis in P388, the latter inhibition occurring a few hours after the inhibition of nucleic acid synthesis. The antibiotic and antitumor activities are destroyed rapidly by ultraviolet light, which gives a product that differs little in amino acid composition, molecular weight, and antigenic property, but can be separated from the native macromomycin by ion exchange chromatography. It is proposed that macromomycin has an ultraviolet-sensitive prosthetic group upon which much of the biological activity is based.
Topics: Amino Acids; Antibiotics, Antineoplastic; Cell Line; DNA; DNA Replication; Kinetics; Spectrophotometry, Ultraviolet; Streptomyces
PubMed: 641069
DOI: No ID Found -
Agricultural and Biological Chemistry Mar 1990A culture similar to Streptomyces variabilis was found to produce a novel cyclic hexadepsipeptide antibiotic named variapeptin. Variapeptin is structurally related to...
A culture similar to Streptomyces variabilis was found to produce a novel cyclic hexadepsipeptide antibiotic named variapeptin. Variapeptin is structurally related to azinothricin, A83586C, and citropeptin. The antibiotic was active against Gram-positive bacteria and showed cytotoxic activity against mammalian cells.
Topics: Amino Acid Sequence; Antibiotics, Antineoplastic; Bacteria; Culture Media; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Sequence Data; Molecular Structure; Peptides, Cyclic; Streptomyces
PubMed: 1368536
DOI: No ID Found -
The Journal of Antibiotics Mar 1981A new antibiotic, stubomycin, was isolated from the culture broth and mycelia of Streptomyces strain No. KG-2245. Stubomycin was prepared as colorless plates and has the...
A new antibiotic, stubomycin, was isolated from the culture broth and mycelia of Streptomyces strain No. KG-2245. Stubomycin was prepared as colorless plates and has the empirical formula C29H35NO5. The antibiotic possesses growth inhibitory activity against Gram-positive bacteria and transplantable murine tumors, such as Ehrlich carcinoma, and leukemia P388. The antibiotic also shows direct cytotoxic activity against HeLa cells in vitro.
Topics: Animals; Antibiotics, Antineoplastic; HeLa Cells; Male; Mice; Molecular Weight; Polyenes; Streptomyces
PubMed: 7275806
DOI: 10.7164/antibiotics.34.259 -
Archives of Disease in Childhood Nov 1994
Review
Topics: Antibiotics, Antineoplastic; Child; Child, Preschool; Drug Administration Schedule; Heart; Humans; Neoplasms; Razoxane; Risk Factors
PubMed: 7826122
DOI: 10.1136/adc.71.5.457 -
Luminamicin, a new antibiotic. Production, isolation and physico-chemical and biological properties.The Journal of Antibiotics Oct 1985A new antibiotic, luminamicin, was isolated from the culture broth of an actinomycete strain OMR-59. It exhibits antibacterial activity against anaerobic bacteria,...
A new antibiotic, luminamicin, was isolated from the culture broth of an actinomycete strain OMR-59. It exhibits antibacterial activity against anaerobic bacteria, especially against Clostridium sp. The molecular formula of the antibiotic was determined as C32H38O12 on the basis of high resolution mass spectrum, elemental analysis and NMR spectrum.
Topics: Actinomycetales; Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bacteria; Fermentation; Lactones; Mice
PubMed: 3840790
DOI: 10.7164/antibiotics.38.1322