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British Medical Journal Mar 1977
Topics: Adult; Daunorubicin; Doxorubicin; Heart Failure; Humans; Leukemia, Myeloid, Acute
PubMed: 265741
DOI: 10.1136/bmj.1.6064.815 -
Carbohydrate Research Jan 1985Reaction of 1,5-anhydro-4-O-benzoyl-2,3,6-trideoxy-3-C-methyl-3-trifluoro-acetami no-L-lyxo-hex-1-enitol with daunomycinone in the presence of anhydrous...
Reaction of 1,5-anhydro-4-O-benzoyl-2,3,6-trideoxy-3-C-methyl-3-trifluoro-acetami no-L-lyxo-hex-1-enitol with daunomycinone in the presence of anhydrous toluene-p-sulfonic acid in benzene, followed by removal of the N- and O-protecting groups under mild conditions, gave 3'-C-methyldaunorubicin. The antitumor activity of the new anthracycline glycoside has been evaluated.
Topics: Animals; Antineoplastic Agents; Daunorubicin; Doxorubicin; Drug Resistance; Leukemia L1210; Leukemia P388; Magnetic Resonance Spectroscopy; Mice; Tumor Stem Cell Assay
PubMed: 3986844
DOI: 10.1016/s0008-6215(00)90775-4 -
Bioorganic & Medicinal Chemistry Dec 2005To study the effects of the sugar structure on the activity of anthracycline against cancer cells, six daunorubicin analogs containing different uncommon sugars were...
To study the effects of the sugar structure on the activity of anthracycline against cancer cells, six daunorubicin analogs containing different uncommon sugars were synthesized. Their cytotoxicities were tested against colon cancer cells by MTS assay. The results showed that the aglycon without sugar moiety has 70-100-fold lower activity against cancer cells than daunorubicin derivatives with various uncommon sugars. It suggests that the sugar structure in daunorubicin plays a critical role in determining its anticancer activity. In the compounds with various sugars, the 4'-OH of the sugar is an important determinant for their activity, while the axial-3'-substituent in the sugar interferes with the binding of daunorubicins to DNA. Therefore, 2,6-dideoxy sugars are a better choice for generating biologically active daunorubicin analogs than 6-deoxysugars, 2,3,6-trideoxysugars, or 2,3,4,6-tetradeoxysugars.
Topics: Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Daunorubicin; Humans; Inhibitory Concentration 50; Molecular Structure
PubMed: 16055335
DOI: 10.1016/j.bmc.2005.06.053 -
Journal of Liposome Research Sep 2011In the present work, a long-circulating epirubicin hydrochloride (EPI)-containing thermosensitive liposome aiming at antitumor therapy, DPPC/MSPC/DSPG/DSPE-mPEG(2000)...
In the present work, a long-circulating epirubicin hydrochloride (EPI)-containing thermosensitive liposome aiming at antitumor therapy, DPPC/MSPC/DSPG/DSPE-mPEG(2000) (EPI-LTSL), was developed and evaluated. Nonthermosensitive and traditional liposomes, HSPC/cholesterol/DSPG/DSPE-mPEG(2000) (EPI-NTSL) and HSPC/cholesterol (EPI-LIP), were also prepared at the same time for comparison. Temperature-dependent EPI release from loaded liposomes in vitro was characterized by the fluorescence method. Different liposome preparations were administered in rats by intravenous injection at the same dosage of 12 mg·kg(-1). EPI and internal standard daunorubicin hydrochloride (DAU) were analyzed by high-performance liquid chromatography and verified by LC tandem mass spectrometry. In the pharmacodynamics study, the EPI-LTSL was combined with local hyperthermia for target-specific delivery to the anesthetized and tumor-bearing mice. According to the in vitro results, more than 90% of loaded EPI was released from MSPC-containing liposome (EPI-LTSL) within 4 minutes at 43°C, while at 37°C, less than 5% was released beyond 60 minutes. However, less than 5% of drug was released at 43°C for the other two liposomes without MSPC (EPI-NTSL and EPI-LIP). The results of the pharmacokinetics study in rats showed that not only the circulation time of EPI was prolonged significantly, but also the concentration in vivo was promoted for EPI-LTSL, compared to EPI-NTSL and EPI-solution. The mean tumor inhibitory rate for EPI-LTSL, EPI-NTSL, and EPI-solution were 61.1, 39.6, and 43.1%, respectively.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Drug Carriers; Epirubicin; Female; Liposomes; Mice; Neoplasm Transplantation; Neoplasms; Rats; Rats, Sprague-Dawley; Temperature; Treatment Outcome
PubMed: 20929434
DOI: 10.3109/08982104.2010.520273 -
Journal of Chromatography Nov 1982A selective and sensitive high-performance liquid chromatographic method was developed for the separation and quantitation of daunorubicin and its metabolites in serum,... (Comparative Study)
Comparative Study
A selective and sensitive high-performance liquid chromatographic method was developed for the separation and quantitation of daunorubicin and its metabolites in serum, plasma, and other biological fluids. Daunorubicin and metabolites in human plasma were injected directly into the high-performance liquid chromatography system via a loop-column to pre-extract the drugs from the plasma, and quantitated against a multilevel calibration curve with adriamycin as the internal standard. The column effluent was monitored with an electrochemical detector at an applied oxidative potential of 0.65 V and by fluorescence. Daunorubicin and four metabolites were separated and characterized by this method. In a blinded evaluation of accuracy and precision, the mean coefficients of variation were 3.8, 3.6 and 9.8% at concentrations of 150, 75 and 15 ng/ml, respectively, and blank samples gave negligible readings. The amperometric sensitivity was greater than achieved by fluorescence detection, and offers an alternative method for quantitation of these compounds. The new method has a limit of detection of less than 2 ng on column, allowing quantitation of less than 10 ng/ml in plasma samples without organic extraction prior to chromatographic analysis.
Topics: Chromatography, High Pressure Liquid; Daunorubicin; Electrochemistry; Humans; Leukemia; Spectrometry, Fluorescence; Time Factors
PubMed: 7153284
DOI: 10.1016/s0378-4347(00)84177-8 -
Cancer Chemotherapy and Pharmacology 1979Experimental data on the pharmacokinetic, toxic and therapeutic properties of daunorubicin-DNA and doxorubicin-DNA complexes are reviewed and summarized as well as the...
Experimental data on the pharmacokinetic, toxic and therapeutic properties of daunorubicin-DNA and doxorubicin-DNA complexes are reviewed and summarized as well as the available reports on clinical trials performed with these anthracycline-DNA complexes. These results are discussed in view of the further development of the drug-carrier concept of cancer chemotherapy.
Topics: Animals; DNA; Daunorubicin; Doxorubicin; Humans; Neoplasms
PubMed: 498424
DOI: 10.1007/BF00253110 -
American Journal of Hospital Pharmacy Apr 1981The stabilities of doxorubicin hydrochloride, daunorubicin hydrochloride, zorubicin, and aclacinomycin A hydrochloride were studied in various infusion fluids at ambient...
The stabilities of doxorubicin hydrochloride, daunorubicin hydrochloride, zorubicin, and aclacinomycin A hydrochloride were studied in various infusion fluids at ambient temperature. Reversed-phase high-pressure liquid chromatographic procedures developed and used in these studies employed internal standards and readily separated each drug from its degradation products. Dilute solutions of the anthracyclines were prepared by appropriate dilutions of the reconstituted solutions of the formulated products with 5% Dextrose Injection, USP (D5W); 0.9% Sodium Chloride Injection, USP (NS); Lactated Ringer's Injection, USP (LR); and Normosol-R pH 7.4. The stability of the anthracyclines was dependent on the pH of the admixture solution which, in turn, was dependent on infusion fluid composition. Daunorubicin and aclacinomycin A exhibited acceptable stability (equal to 90% of the original concentration) in D5W, NS, and LR for more than 48 hours. Doxorubicin manifested similar stability in the first two fluids. Zorubicin showed similar stability only in Normosol-R pH 7.4 fluid for 22 hours.
Topics: Aclarubicin; Antibiotics, Antineoplastic; Chromatography, High Pressure Liquid; Daunorubicin; Doxorubicin; Drug Stability; Hydrogen-Ion Concentration; Infusions, Parenteral; Naphthacenes; Pharmacopoeias as Topic; United States
PubMed: 6945043
DOI: No ID Found -
The Journal of Antibiotics Dec 19843'-Deamino-4'-epi-3'-hydroxy-daunorubicin (11) and -doxorubicin (14) have been synthesized. In the in vivo murine P-388 lymphocytic leukemia assay, these two compounds...
3'-Deamino-4'-epi-3'-hydroxy-daunorubicin (11) and -doxorubicin (14) have been synthesized. In the in vivo murine P-388 lymphocytic leukemia assay, these two compounds were more active than daunorubicin (1) and doxorubicin (2), respectively. Comparative studies in the P-388 assay indicated 3'-deamino-3'-hydroxydoxorubicin (3) to be more active than its 4'-epimer 14.
Topics: Animals; Daunorubicin; Doxorubicin; Epirubicin; Leukemia P388; Mice; Structure-Activity Relationship
PubMed: 6549317
DOI: 10.7164/antibiotics.37.1635 -
Journal of Clinical Pharmacology 1986Anthracycline antibiotics remain among the most potent anticancer drugs, but their efficacy is limited by the development of a dose-dependent irreversible cardiomyopathy... (Clinical Trial)
Clinical Trial Review
Anthracycline antibiotics remain among the most potent anticancer drugs, but their efficacy is limited by the development of a dose-dependent irreversible cardiomyopathy and by the emergence of clones of tumor cells resistant to the effects of the drug. Modifications of the basic anthracycline structure have resulted in molecules that may share the activity of the parent compound, with amelioration of some toxicities, absence of cross-resistance, or activity against tumors insensitive to the parent drug. Epirubicin has a unique metabolic pathway, glucuronidation, that may result in more rapid plasma clearance and reduced toxicity as compared with doxorubicin. Epirubicin has demonstrated comparable activity to doxorubicin in breast cancer, with possibly reduced toxicity. Idarubicin is of interest because of its cytotoxic activity when given orally. Idarubicin has prolonged retention in the plasma and has equal cytotoxic activity to the parent compound. Idarubicin has demonstrated activity against acute leukemia and breast cancer; in the latter tumor category, some doxorubicin-resistant tumors have responded. Esorubicin is of interest because of its nearly absent cardiac toxicity. This agent has some activity against solid tumors and is currently being clinically tested. Aclacinomycin A is an anthracycline in which a trisaccharide is substituted for the aminosugar. Aclacinomycin A and the related compound marcellomycin are of interest as both cytotoxic and differentiating agents. Menogaril is an anthracycline with the aminosugar on the D ring; it does not exhibit cross-resistance with doxorubicin or cardiotoxicity. Mitoxantrone is a compound that is related to the anthracyclines but has a different mechanism of action. This agent has significant activity against acute leukemia and breast cancer and is currently being compared with doxorubicin. Amsacrine is another compound related to the anthracyclines that possesses major activity against acute leukemias. Minor modifications of the anthracycline molecule have had major impact on the biologic activity of these drugs. New anthracycline analogues with up to 100 times the potency of currently available anthracyclines are being developed for clinical testing, and these complex molecules retain a nearly unlimited potential for structural modification.
Topics: Aclarubicin; Amsacrine; Animals; Antibiotics, Antineoplastic; Clinical Trials as Topic; Daunorubicin; Doxorubicin; Drug Evaluation, Preclinical; Epirubicin; Humans; Idarubicin; Kinetics; Menogaril; Mitoxantrone; Naphthacenes; Neoplasms; Nogalamycin; Rabbits
PubMed: 2944917
DOI: 10.1002/j.1552-4604.1986.tb02942.x -
Folia Microbiologica 1978
Review
Topics: Animals; Antibiotics, Antineoplastic; Bacteria; Chemical Phenomena; Chemistry; Daunorubicin; Doxorubicin; Glycosides; Humans; Naphthacenes; Neoplasms; Nogalamycin
PubMed: 348587
DOI: 10.1007/BF02915316