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Cancer Nursing Dec 1980
Clinical Trial
Topics: Clinical Trials as Topic; Daunorubicin; Humans; Neoplasms
PubMed: 7000336
DOI: No ID Found -
Molecules (Basel, Switzerland) Dec 2020A new approach for the sensitive, robust and rapid determination of idarubicin (IDA) in human plasma and urine samples based on liquid chromatography with fluorescence...
A new approach for the sensitive, robust and rapid determination of idarubicin (IDA) in human plasma and urine samples based on liquid chromatography with fluorescence detection (LC-FL) was developed. Satisfactory chromatographic separation of the analyte after solid-phase extraction (SPE) was performed on a Discovery HS C18 analytical column using a mixture of acetonitrile and 0.1% formic acid in water as the mobile phase in isocratic mode. IDA and daunorubicin hydrochloride used as an internal standard (I.S.) were monitored at the excitation and emission wavelengths of 487 and 547 nm, respectively. The method was validated according to the FDA and ICH guidelines. The linearity was confirmed in the range of 0.1-50 ng/mL and 0.25-200 ng/mL, while the limit of detection (LOD) was 0.05 and 0.125 ng/mL in plasma and urine samples, respectively. The developed LC-FL method was successfully applied for drug determinations in human plasma and urine after oral administration of IDA at a dose of 10 mg to a patient with highly advanced alveolar rhabdomyosarcoma (RMA). Moreover, the potential exposure to IDA present in both fluids for healthcare workers and the caregivers of patients has been evaluated. The present LC-FL method can be a useful tool in pharmacokinetic and clinical investigations, in the monitoring of chemotherapy containing IDA, as well as for sensitive and reliable IDA quantitation in biological fluids.
Topics: Antibiotics, Antineoplastic; Chromatography, Liquid; Daunorubicin; Drug Monitoring; Fluorescence; Humans; Idarubicin; Limit of Detection; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction
PubMed: 33316898
DOI: 10.3390/molecules25245799 -
The Journal of Physical Chemistry... May 2024Daunomycin is a widely used anticancer drug, yet the mechanism underlying how it binds to DNA remains contested. 469 all-atom trajectories of daunomycin binding to the...
Daunomycin is a widely used anticancer drug, yet the mechanism underlying how it binds to DNA remains contested. 469 all-atom trajectories of daunomycin binding to the DNA oligonucleotide (GCG CAC GTG CGC) were collected using weighted ensemble (WE)-enhanced sampling. Mechanistic insights were revealed through analysis of the ensemble of trajectories. Initially, the binding process involves a ubiquitous hydrogen bond between the DNA backbone and the NH group on daunomycin. During the binding process, most trajectories exhibited similar structural changes to DNA, including DNA base pair rise, bending, and minor groove width changes. Variability within the ensemble of binding trajectories illuminates differences in the orientation of daunomycin as it initially intercalates; around 10% of trajectories needed minimal rearrangement from intercalation to reaching the fully bound configuration, whereas most needed an additional 1-5 ns to rearrange. The results here emphasize the utility of generating an ensemble of trajectories to discern biomolecular binding mechanisms.
Topics: DNA; Daunorubicin; Intercalating Agents; Molecular Dynamics Simulation; Nucleic Acid Conformation; Hydrogen Bonding
PubMed: 38776167
DOI: 10.1021/acs.jpclett.4c00961 -
Nature: New Biology Sep 1972
Topics: Animals; Cells, Cultured; DNA; Daunorubicin; Drug Combinations; Injections, Intravenous; Leukemia, Experimental; Leukemia, Myeloid; Lysosomes; Mice; Mice, Inbred DBA; Mice, Inbred Strains; Pinocytosis; Protein Binding; Sarcoma, Experimental; Staphylococcus
PubMed: 4507516
DOI: 10.1038/newbio239110a0 -
International Journal of Molecular... Feb 2021The use of peptide-drug conjugates has generated wide interest as targeted antitumor therapeutics. The anthracycline antibiotic, daunomycin, is a widely used anticancer...
The use of peptide-drug conjugates has generated wide interest as targeted antitumor therapeutics. The anthracycline antibiotic, daunomycin, is a widely used anticancer agent and it is often conjugated to different tumor homing peptides. However, comprehensive analytical characterization of these conjugates via tandem mass spectrometry (MS/MS) is challenging due to the lability of the O-glycosidic bond and the appearance of MS/MS fragment ions with little structural information. Therefore, we aimed to investigate the optimal fragmentation conditions that suppress the prevalent dissociation of the anthracycline drug and provide good sequence coverage. In this study, we comprehensively compared the performance of common fragmentation techniques, such as higher energy collisional dissociation (HCD), electron transfer dissociation (ETD), electron-transfer higher energy collisional dissociation (EThcD) and matrix-assisted laser desorption/ionization-tandem time-of-flight (MALDI-TOF/TOF) activation methods for the structural identification of synthetic daunomycin-peptide conjugates by high-resolution tandem mass spectrometry. Our results showed that peptide backbone fragmentation was inhibited by applying electron-based dissociation methods to conjugates, most possibly due to the "electron predator" effect of the daunomycin. We found that efficient HCD fragmentation was largely influenced by several factors, such as amino acid sequences, charge states and HCD energy. High energy HCD and MALDI-TOF/TOF combined with collision induced dissociation (CID) mode are the methods of choice to unambiguously assign the sequence, localize different conjugation sites and differentiate conjugate isomers.
Topics: Amino Acid Sequence; Daunorubicin; Electron Transport; Peptides; Protein Conformation; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
PubMed: 33562082
DOI: 10.3390/ijms22041648 -
Journal of Pharmaceutical and... Sep 2018A simple, rapid, reliable and sensitive method based on liquid chromatography with fluorescence detection (LC-FL) for the quantification of doxorubicin (DOX) in human...
A simple, rapid, reliable and sensitive method based on liquid chromatography with fluorescence detection (LC-FL) for the quantification of doxorubicin (DOX) in human plasma and urine samples was developed. The assay was carried out after the solid-phase extraction procedure (SPE) with hydrophilic-lipophilic balance (HLB) cartridges, and with daunorubicin hydrochloride (DAU) used as the internal standard. Chromatographic separation was performed on a Discovery HS C18 column in isocratic elution mode, and the detection of the analytes set at excitation and emission wavelengths of 487 and 555 nm, respectively. The developed LC-FL method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification for DOX were 0.5 and 1 ng/mL in both biological fluids, respectively. Linearity was confirmed in the range of 1-1000 ng/mL and 0.001-25 μg/mL in plasma and urine samples, respectively, with a correlation coefficient greater than 0.9994. The proposed LC-FL method is selective, precise and accurate, and has been successfully applied for drug monitoring in pediatric cancer patients treated with DOX as a component of OEPA (Oncovin (Vincristine)-Etoposide-Prednisone-Adriamycin) and IOA (Ifosfamide-Oncovin-Adriamycin) chemotherapeutic schemes. Moreover, real exposure of hospital personnel to the anthracycline drugs in plasma and urine was evaluated in clinical practice.
Topics: Adolescent; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chromatography, High Pressure Liquid; Daunorubicin; Doxorubicin; Drug Monitoring; Etoposide; Fluorescence; Humans; Limit of Detection; Male; Neoplasms; Occupational Exposure; Personnel, Hospital; Prednisone; Reproducibility of Results; Solid Phase Extraction; Vincristine
PubMed: 29936377
DOI: 10.1016/j.jpba.2018.06.031 -
European Journal of Biochemistry Sep 2004We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the...
We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin antibiotic WP631 with DNA. The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin. Footprints are found in a diverse range of sequences, many of which are rich in GT (AC) or GA (TC) residues. As expected, the ligand binds well to the sequences CGTACG and CGATCG, but clear footprints are also found at hexanucleotide sequences such GCATGC and GCTAGC. The various footprints do not contain any particular unique di-, tri- or tetranucleotide sequences, but are frequently contain the sequence (G/C)(A/T)(A/T)(G/C). All sequences with this composition are protected by the ligand, though it can also bind to some sites that differ from this consensus by one base pair.
Topics: Antibiotics, Antineoplastic; Base Sequence; Binding Sites; DNA; DNA Footprinting; Daunorubicin; Diethyl Pyrocarbonate; Hydroxyl Radical; Molecular Structure; Potassium Permanganate
PubMed: 15317591
DOI: 10.1111/j.0014-2956.2004.04292.x -
Journal of Chromatography Jun 1978A method is given for the determination of daunorubicin and its main metabolite, daunorubicinol, in plasma from leukemic patients after administration of daunorubicin as...
A method is given for the determination of daunorubicin and its main metabolite, daunorubicinol, in plasma from leukemic patients after administration of daunorubicin as the free drug or as a complex with DNA. Daunorubicin and daunorubicinol are extracted from 2 ml of plasma (pH 8.1) using a mixture of chloroform and 1-heptanol (9:1). After re-extraction into phosphoric acid (0.1 M), the separation is performed as reversed phase liquid chromatography on a LiChrosorb RP-2 (5 micrometer) column with a mobile phase of acetonitrile-water, acidified with phosphoric acid. The precision, by quantitation with a photometric detector, was better than 2% within the range 20 ng/ml to 200 ng/ml. Some determinations of plasma levels of daunorubicin and daunorubicinol are presented.
Topics: Chromatography, Gas; Daunorubicin; Dose-Response Relationship, Drug; Leukemia; Solvents
PubMed: 659557
DOI: 10.1016/s0021-9673(00)89874-x -
In Vivo (Athens, Greece) 2007In the search for new derivatives of daunorubicin with high activity and/or the ability to overcome the drug resistance barrier of cancer cells, some new analogs of...
In the search for new derivatives of daunorubicin with high activity and/or the ability to overcome the drug resistance barrier of cancer cells, some new analogs of amidino-daunorubicin, containing the chiral substituent in the formamidine group (-N=CH-N<) at the C-3' position of daunosamine moiety, have been synthesized. In order to estimate the influence of the configuration of the chiral group on the biological properties of the new derivatives of daunorubicin, three chiral amines, namely 1-cyclohexyl-ethylamine, 1-phenylethylamine and N-methyl-l-phenyl-ethylamine, both R and S isomers and their racemates, were used. These new compounds were tested for their cytotoxic activity in vitro against the cells of A549, SW707, T47D and HCV29T cancer lines. The resistance index (RI) values were obtained using the cells of the sensitive LoVo, MES-SA, HL-60 human cancer cell lines, as well as their resistant sublines (LoVo/Dx, MES-SAIDX5 and HL-60/MX2, respectively). All obtained derivatives appeared to be able to overcome the drug resistance barrier of cancer cells.
Topics: Antibiotics, Antineoplastic; Cell Division; Cell Line, Tumor; Daunorubicin; HL-60 Cells; Humans
PubMed: 17436596
DOI: No ID Found -
The Journal of Organic Chemistry Apr 2007The anthracycline antibiotics daunorubicin and doxorubicin have been used widely as anticancer drugs, but their cardiotoxicity limits their clinical use. We describe...
The anthracycline antibiotics daunorubicin and doxorubicin have been used widely as anticancer drugs, but their cardiotoxicity limits their clinical use. We describe here the preparation of a small panel of daunorubicin analogues in which the anthraquinone core is replaced with simpler aromatic moieties that lack a quinone functionality. The targets consist of a functionalized 1,2,3,4-tetrahydro-naphthalene or 1,2,3,4-tetrahydro-anthracene core bound to one of three monosaccharides: daunosamine, acosamine, or 4-amino-2,3,6-trideoxy-l-threo-hexopyranose. Key steps in the synthesis included an enantioselective ring opening of benzo-fused norbornene derivatives for the preparation of the core structures and the use of silver hexafluorophosphate-promoted thioglycoside activation in the glycosylation of these cores. Evaluation of these compounds against the MCF-7 cancer cell line demonstrated that the identity of the carbohydrate moiety appeared to have little influence on the cytotoxicity. Moreover, the analogues with the 1,2,3,4-tetrahydro-naphthalene core showed no cytotoxicity, while those possessing the 1,2,3,4-tetrahydro-anthracene moiety were more active. The IC50 values for the latter group of compounds were in the range of 94-134 microM, compared to 17 microM for doxorubicin and 5 microM for daunorubicin.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Daunorubicin; Drug Screening Assays, Antitumor; Humans; Monosaccharides; Structure-Activity Relationship
PubMed: 17373847
DOI: 10.1021/jo062542q