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Annals of the New York Academy of... 1978Actinomycin D, when encapsulated within liposomes, has been previously shown to be less toxic to mice than nonencapsulated actinomycin D, but to retain its tumoricidal...
Actinomycin D, when encapsulated within liposomes, has been previously shown to be less toxic to mice than nonencapsulated actinomycin D, but to retain its tumoricidal activity. We have compared the toxic effects of Act D encapsulated either in the aqueous phase or in the lipid phase of liposomes (APL and LPL, respectively), and the nonencapsulated Act D on the blood forming system, on cell proliferation in the intestine, and on antibody production by spleen lymphocytes. At a single dose of 0.4 mg/kg, APL-encapsulated Act D wass less toxic to white blood cells and to the nucleated cells and colony-forming stem cells of the bone marrow. During toxicity in the proliferating intestinal cells, measured by 3H-thymidine incorporation, was reduced by about a factor of 4 with encapsulation in APL, particularly 24 hours after Act D administration. The toxiciaty of LPL-encapsulated Act D to both the blood-forming system and the intestinal proliferating cells was, however, not significantly different from that of the nonencapsulated Act D. Effects of Act D on the antibody production by spleen cells, determined by the "limited hemolysis in agar" assay, showed that immunosuppression was most markedly reduced by liposome encapsulation either in APL or in LPL, when the drug was given one day before the antigen. These findings are important for considerations of liposome application in cancer chemotherapy.
Topics: Animals; Antibody Formation; Bone Marrow; Dactinomycin; Intestinal Mucosa; Liposomes; Mice; Spleen
PubMed: 279296
DOI: 10.1111/j.1749-6632.1978.tb22033.x -
Applied Microbiology and Biotechnology Aug 2012In the course of our screening program for anti-Mycobacterium bovis bacillus Calmette-Guérin (BCG) and anti-Mycobacterium tuberculosis H37Rv (MTB H37Rv) agents from our...
In the course of our screening program for anti-Mycobacterium bovis bacillus Calmette-Guérin (BCG) and anti-Mycobacterium tuberculosis H37Rv (MTB H37Rv) agents from our marine natural product library, a newly isolated actinomycete strain, designated as MS449, was picked out for further investigation. The strain MS449, isolated from a sediment sample collected from South China Sea, produced actinomycin X(2) and actinomycin D in substantial quantities, which showed strong inhibition of BCG and MTB H37Rv. The structures of actinomycins were elucidated by nuclear magnetic resonance and mass spectrometric analysis. The strain MS449 was taxonomically characterized on the basis of morphological and phenotypic characteristics, genotypic data, and phylogenetic analysis. The 16S rRNA gene sequence of the strain was determined and a database search indicated that the strain was closely associated with the type strain of Streptomyces avermitilis (99.7 % 16S rRNA gene similarity). S. avermitilis has not been previously reported to produce actinomycins. The marine-derived strain of Streptomyces sp. MS449 produced notably higher quantities of actinomycin X(2) (1.92 mg/ml) and actinomycin D (1.77 mg/ml) than previously reported actinomycins producing strains. Thus, MS449 was considered of great potential as a new industrial producing strain of actinomycin X(2) and actinomycin D.
Topics: Antitubercular Agents; Base Sequence; Culture Media; DNA Primers; Dactinomycin; Fermentation; Marine Biology; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; RNA, Ribosomal, 16S; Streptomyces
PubMed: 22543353
DOI: 10.1007/s00253-012-4079-z -
Rapid Communications in Mass... Dec 2010A rapid and reliable method has been optimized and established for the analysis of the metabolites from a marine actinomycete by high-performance liquid chromatography...
Rapid screening and characterization of metabolites from a marine-derived actinomycete by high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry.
A rapid and reliable method has been optimized and established for the analysis of the metabolites from a marine actinomycete by high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC/QTOF MS/MS). From MS/MS spectra, the product ions of [M + H](+) were recorded to provide abundant structural information of the mother nucleus and peptide moieties. Using the QTOF MS/MS and in-source collision-induced dissociation (in-source CID) techniques, three main metabolites including actinomycin D, actinomycin V and actinomycin I were determined and characterized by elemental compositions of precursor and product ions (<7 ppm). Additionally, this method provided information about the compositions of the peptide residues and the sequences of the amino acid from a series of fragment ions. It proved useful for the identification of the metabolites in marine samples which have similar structures especially when there were no reference compounds available.
Topics: Actinobacteria; Antibiotics, Antineoplastic; Chromatography, High Pressure Liquid; Dactinomycin; Hep G2 Cells; Humans; Molecular Structure; Seawater; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 21072796
DOI: 10.1002/rcm.4744 -
Nuclear Medicine Communications Dec 2018Dactinomycin is a well-known antitumor-antibiotic drug isolated from soil bacterium Streptomyces, which exhibits broad-spectrum pharmacological and biochemical effects....
Synthesis and preclinical evaluation of bactericidal agent isolated from soil bacterium (Streptomyces): a novel diagnostic technique to enhance anticancer efficacy through radiosynthesis.
OBJECTIVES
Dactinomycin is a well-known antitumor-antibiotic drug isolated from soil bacterium Streptomyces, which exhibits broad-spectrum pharmacological and biochemical effects. In this study, dactinomycin was successfully labeled with technetium-99m for early diagnosis of bacterial infection and to discriminate it from acute inflammation.
MATERIALS AND METHODS
Various labeling parameters such as pH, ligand concentration, reducing agent, and stabilizing agent were investigated. Radio-TLC technique was used to calculate percent radiochemical purity of radiopharmaceutical. Characterization studies were carried out using electrophoresis and radio-high-performance liquid chromatography techniques. Furthermore, saline and serum stability studies were performed to investigate biocompatibility. Biodistribution and scintigraphy studies were performed in infected and inflamed animal models to discriminate between bacterial infections (Escherichia coli and Staphylococcus aureus) and acute inflammations (heat-killed S. aureus).
RESULTS
The results demonstrated that the highest radiochemical purity of at least 95% was achieved using 100-500 µg ligand and 3-8 µg SnCl2·2H2O as reducing agent at 4-9 pH. Technetium-99m-dactinomycin (Tc-DTN) was observed clearly bounded to the infection site having target/nontarget ratio 2.96±0.64 at 30 min after administration, which increased to 5.21±1.03 at 4 h after administration. Further accumulation was seen in heart, lungs, liver, stomach, kidneys, spleen, and intestine. An in-vitro cell-binding study was also performed, which showed high binding affinity of Tc-DTN with S. aureus-induced infectious lesions.
CONCLUSION
Tc-DTN can easily be synthesized using standardized optimization conditions. The radiopharmaceutical has the highest accumulation potential at targeted site induced by S. aureus without any prominent in-vivo cytotoxicity. Tc-DTN may be used as a potential diagnostic agent to locate S. aureus-induced infection lesions at an early stage. Tc-DTN can successfully discriminate between infection and inflammatory models which cannot be achieved from other radiopharmaceuticals developed in the past few decades.
Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Chemistry Techniques, Synthetic; Dactinomycin; Drug Stability; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Isotope Labeling; Kinetics; Ligands; Male; Mice; Radiochemistry; Soil Microbiology; Staphylococcal Infections; Streptomyces; Technetium; Tin Compounds; Tissue Distribution
PubMed: 30256273
DOI: 10.1097/MNM.0000000000000916 -
Rapid Communications in Mass... Feb 2022A series of photodegradation impurities and a series of degradation impurities produced in autoclaving in xinfujunsu injection were discovered, and these unknown...
Separation and characterization of two series of unknown degradation impurities caused by light irradiation and autoclaving in xinfujunsu injection using liquid chromatography tandem mass spectrometry.
RATIONALE
A series of photodegradation impurities and a series of degradation impurities produced in autoclaving in xinfujunsu injection were discovered, and these unknown impurities were separated and characterized thoroughly using liquid chromatography tandem quadrupole time-of-flight mass spectrometry.
METHODS
The column was a Platisil 5 μm ODS (4.6 × 250 mm, 5 μm). For the analysis of degradation impurities caused by light irradiation and autoclaving, the mobile phase was composed of 0.01 M ammonium formate aqueous solution and acetonitrile/isopropanol (90:10, V/V). Full scan LC-MS and LC-MS was carried out to obtain as much structural information as possible. The fragmentation behavior of actinomycin D, actinomycin S , and its impurities was studied and used to obtain information about the structures of these impurities.
RESULTS
Based on MS spectral data and exact mass measurements, the chemical structures of two series of degradation impurities were characterized, among which five unknown impurities were photodegradation impurities and seven unknown impurities were degradation impurities produced in autoclaving of xinfujunsu injection.
CONCLUSIONS
Based on characterization of impurities, this study also revealed the cause of impurity production and provided guidance for enterprises to improve the process and drug packaging material to reduce impurity content. Furthermore, this study also provided scientific basis for further improvement of official monographs in pharmacopoeias.
Topics: Chromatography, High Pressure Liquid; Dactinomycin; Drug Contamination; Drugs, Chinese Herbal; Hot Temperature; Light; Photolysis; Tandem Mass Spectrometry
PubMed: 34773922
DOI: 10.1002/rcm.9223 -
Comptes Rendus Des Seances de La... 1974
Topics: Animals; Annelida; Dactinomycin; Dose-Response Relationship, Drug; Fasting; Regeneration; Time Factors
PubMed: 4282319
DOI: No ID Found -
The Journal of Physical Chemistry. B Nov 2020NMR studies have indicated that the anti-tumor therapeutic agent actinomycin D (ACTD) can induce seemingly single-stranded DNA (ssDNA) oligomer 5'-CCGTTGTGG-3' to form a...
NMR studies have indicated that the anti-tumor therapeutic agent actinomycin D (ACTD) can induce seemingly single-stranded DNA (ssDNA) oligomer 5'-CCGTTGTGG-3' to form a hairpin structure with tandem GT mismatches at the stem region next to a loop of three stacked thymine bases. In an effort to uncover the preference of binding sequence and to elucidate the thermodynamics properties of the binding, a combination of spectroscopic techniques and computational simulation studies was performed with d(CCGTTGTGG) and d(CCGAAGAGG) (denoted as GTT and GAA, respectively; = 3, 5, and 7) sequences. In the presence of 7-amino actinomycin D (7AACTD), all the six oligomers formed stable hairpin structures. The GTT-7AACTD/GAA-7AACTD hairpin structure was more stable than the corresponding GTT-7AACTD and GAA-7AACTD ( = 3, 7). No significant Δ difference was observed between GTT-7AACTD and GAA-7AACTD complexes with the same loop length. In agreement with the 7AACTD-induced hairpin stability results, the binding affinity of GTT and GAA with 7AACTD increased from = 3 to = 5 and then decreased when is 7. Moreover, GTT and GAA with the same loop length showed comparable binding affinities to 7AACTD. Furthermore, molecular dynamics simulations found that van der Waals interactions between GTT/GAA and 7AACTD were the primary attractive forces for 7AACTD binding, and the electrostatic interactions between the carbonyl groups of 7AACTD and bases in the hairpin were the major unfavorable forces. These findings furthered our understanding that 7AACTD is sensitive to the loop size and sequence as well as tandem GT/GA mismatches of their deoxyribonucleic acid (DNA) targets. A deep understanding of the thermodynamics and the molecular recognition mechanism of 7AACTD with ssDNAs would further the development of ACTD-like antitumor agents.
Topics: Base Sequence; DNA, Single-Stranded; Dactinomycin; Nucleic Acid Conformation; Thermodynamics
PubMed: 33136398
DOI: 10.1021/acs.jpcb.0c05593 -
Food and Chemical Toxicology : An... Sep 2018Actinomycetes are main producers of antibiotics and targeted screening could improve the efficiency of discovering new drugs. This study describes, for the first time,...
Purification and identification of an actinomycin D analogue from actinomycetes associated with Ganoderma applanatum via magnetic molecularly imprinted polymers and tandem mass spectrometry.
Actinomycetes are main producers of antibiotics and targeted screening could improve the efficiency of discovering new drugs. This study describes, for the first time, the isolation of endophytic actinomycetes from the macrofungus Ganoderma applanatum. To increase the efficiency of screening, novel actinomycin D (Act D) molecularly-imprinted polymers were adsorbed to the surface of FeO@SiO magnetic microspheres (MMIPs) and using in the isolation. A monolithic column prepared with magnetic molecularly imprinted polymers was employed to adsorb actinomycin D and its analogues for selective analysis and identification via MS/MS spectroscopy. The MMIP-monolithic column was selective for the structural features of Act D and its analogue, and the maximum loading of the MMIPs for Act D was ∼23.5 μg/g. The recognition time of the Act D was 20-30 min and had good discriminative ability. A new analogue was identified from endophytic actinomycetes KLBMP 2541, and it was purified using MMIPs comparison with MMIPs-solid phase extraction. Structural identification analysis confirmed that the new analogue was 2-methyl-actinomycin D, which has better anti-tumor activity than Act D. The presented method combines the advantages of MMIPs and MS with popular solutions to enable high affinity and selectivity screening of specific antibiotics from endophytic actinomycetes.
Topics: Cell Line, Tumor; Dactinomycin; Ferrous Compounds; Ganoderma; Humans; Magnetite Nanoparticles; Microscopy, Electron, Scanning; Molecular Imprinting; Molecular Structure; Polymers; Tandem Mass Spectrometry
PubMed: 29777719
DOI: 10.1016/j.fct.2018.05.015 -
Annals of the New York Academy of... Oct 1960
Topics: Animals; Cell Line; Dactinomycin; HeLa Cells; Humans; In Vitro Techniques; Neoplasms, Experimental
PubMed: 13706673
DOI: 10.1111/j.1749-6632.1960.tb20171.x -
Proceedings of the National Academy of... Aug 1966
Topics: Centrifugation, Density Gradient; Culture Techniques; Dactinomycin; RNA, Viral; Semliki forest virus
PubMed: 5229967
DOI: 10.1073/pnas.56.2.440