- 1H NMR structural and thermodynamical analysis of the hetero-association of daunomycin and novatrone in aqueous solution
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The complexation of antitumour antibiotics novatrone (NOV) and daunomycin (DAU) in aqueous solution has been studied by one- and two-dimensional 1H-NMR spectroscopy (500 MHz) in order to elucidate the probable molecular mechanism of the action
- Veselkov,Evstigneev,Rozvadovskaya,Hernandez Santiago,Zubchenok,Djimant,Davies
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Read Online
- Synthesis of new maleimide derivatives of daunorubicin and biological activity of acid labile transferrin conjugates
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Maleimide groups were bound to the 3'-amino position of daunorubicin through a benzamide bond or to the 13-keto position through a benzoyl hydrazone or phenylacetyl hydrazone bond. The acid labile transferrin conjugates prepared with the latter two derivatives exhibited high activity in human melanoma cells (MEXF 989) using a clonogenic cell assay comparable to or exceeding that of daunorubicin.
- Kratz, Felix,Beyer, Ulrich,Schumacher, Peter,Krueger, Michael,Zahn, Heike,Roth, Thomas,Fiebig, Heinz H.,Unger, Clemens
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Read Online
- Synthesis and Antiproliferative Activity of Conjugates of Anthracycline Antibiotics with Sesquiterpene Lactones of the Elecampane
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The daunorubicin and doxorubicin anthracycline antibiotics were modified with the Inula helenium L. sesquiterpene lactones (alantolactone, isoalantolactone, and alloalantolactone) and with their epoxy derivatives. Antiproliferative properties of these conjugates were studied on tumor and normal cell lines. The daunorubicin conjugates with the sesquiterpene lactones (isoalantolactone, allantolactone, and alloalantolactone) and with their epoxy derivatives were found to exhibit the higher activity against human tumor cell lines than the corresponding doxorubicin conjugates. The daunorubicin conjugate with epoxyisoalantolactone proved to be the most effective compound, because it was more cytotoxic than daunorubicin towards a number of cell lines, including those daunorubicin-resistant, and did not affect normal human cells.
- Semakov,Anikina,Afanasyeva,Pukhov,Klochkov
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p. 538 - 546
(2018/10/24)
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- Block copolymers for stable micelles
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The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.
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(2013/11/19)
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- THERAPEUTIC FOR HEPATIC CANCER
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A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
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- METHOD OF DERIVATISING AN ANALYTE FOR SUBSEQUENT DETECTION THROUGH A NUCLEIC ACID BASED SENSOR
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A method of derivatising an analyte for subsequent detection through a nucleic acid based sensor and a sensor based thereon.
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- Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
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- Immune Modulating Oligonucleotides in Connection with Chemotherapeutic Measures
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The invention relates to the use of immune modulators on the basis of DNA in the form of covalently closed nucleic acid molecules comprising immune stimulatory sequence motifs, for the production of a pharmaceutical for the therapeutic treatment of tumor diseases in combination with chemotherapeutic drugs.
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- TARGETED DRUG DELIVERY USING SULFONAMIDE DERIVATIVES
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The present invention relates to Glutathione S-transferase (GST)/Reduced Glutathione (GSH) as a means for the in-vivo release of a drug that has been conjugated to specific electrophilic moieties via a sulfonamide bond. The drug may be an anticancer agent (or one with other therapeutic properties) carrying a free —NH— which has been derivatized by the attachment of an electrophile containing a moiety, such as p-CN— or p-NO 2-pyridinylsulfonyl groups, or p-NO 2- or 2,4 dinitrophenylsulfonyl groups, or suitable derivatives thereof, to make a prodrug. Optionally, the sulfonamide moiety may have attached to it a targeting molecule. The present invention also provides Glutathione S-transferase (GST)/Reduced Gluthathione (GSH) as a means for the release of a protected amino derivative that has been conjugated to specific electrophilic moieties via a sulfonamide bond. The precursor is a synthetic intermediate carrying a free —NH— which has been derivatized by the attachment of an electrophile via a sulfonamide bond.
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- 13-dihydro-3′ aziridino anthracyclines
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The present invention relates to anthracycline glycosides, to a process for their preparation and to pharmaceutical compositions containing the same.
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- A daunorubicin β-galactoside prodrug for use in conjunction with gene- directed enzyme prodrug therapy
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N-[4-(β-D-Galactopyranosyl)-3-nitrobenzyloxycarbonyl]daunomycin was synthesized as a neutral prodrug of daunomycin. Although stable in 0.05 M phosphate buffer, pH 7.4 at 37°C, it was rapidly converted to daunomycin and 3-nitro-4-hydroxybenzyl alcohol under the same conditions in the presence of E. coli β-galactosidase. (C) 2000 Elsevier Science Ltd.
- Ghosh, Ajit K.,Khan, Saeed,Marini, Frank,Nelson, J. Arly,Farquhar, David
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p. 4871 - 4874
(2007/10/03)
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- Novel anthracycline-spacer-β-glucuronide, -β-glucoside, and -β-galactoside prodrugs for application in selective chemotherapy
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A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-β-glycoside were designed to be activated by β-glucuronidase or β-galactosidase. Prodrugs with -chloro, -bromo or -n-hexyl substituents on the spacer were synthesized as well as prodrugs containing a -β-glucuronyl, -β-glucosyl or -β-galactosyl carbamate specifier. The key step in the synthesis of all prodrugs is the highly β-diastereoselective addition reaction of the anomeric hydroxyl of a glycosyl donor to a spacer isocyanate resulting in the respective β-glycosyl carbamate pro-moieties. The resulting protected pro-moieties were coupled to an anthracycline. Prodrugs were evaluated with respect to activation rate by the appropriate enzyme and additionally, their IC50 values were determined. Optimal prodrugs in this study were at least 100- to 200-fold less toxic than their corresponding drug in vitro and were activated to the parent drug in a half-life time of approximately 2h. Copyright (C) 1999 Elsevier Science Ltd.
- Leenders, Ruben G. G.,Damen, Eric W. P.,Bijsterveld, Edward J. A.,Scheeren, Hans W.,Houba, Pieter H. J.,Van Der Meulen-Muileman, Ida H.,Boven, Epie,Haisma, Hidde J.
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p. 1597 - 1610
(2007/10/03)
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- Compositions containing piperine
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A pharmaceutical composition having increased bioavailability characterized by piperine of the formula STR1 and a drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
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- Glycosylated prodrugs, their method of preparation and their uses
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Glycosylated prodrugs, a preparation method therefor, and their use with tumor-specific immunoenzymatic conjugates for the treatment of cancer, are described. These anthracycline prodrugs have formula (I). STR1
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- Compositions containing piperine
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A pharmaceutical composition having increased bioavailability characterized by piperine of the formula and a drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
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- Liposome composition whose liposome membrane contains a polyoxyethylene derivative
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A liposome composition is obtained by using as constituent components of the liposome membrane a polyoxyethylene derivative represented by the general formula: wherein X represents an alkanoyl group or an alkyl group, Y represents a residue of a compound having a negative charge, and n is an integer of 2 to 50, and a phospholipid. The liposome composition has good dispersibility, high drug-encapsulation property and high stability.
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- Amino acid and hydroxyamino acid transporter compounds for therapeutic applications, process and use
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Amino acid and hydroxyamino acid transporter compounds are provided, in which an amino acid or hydroxyamino acid as a carrier is linked via an ester linkage to a therapeutic compound, and having one of the general formulae: in which AA represents the amino acid or hydroxyamino acid, HAA represents the hydroxyamino acid, and Z1 and Z2 represent a therapeutic compound, or a linking compound attached to COOH or OH of the hydroxyamino acid and to the therapeutic compound, as well as a process for preparing the same, and a process for administration of the same to animals, to obtain the benefit of the therapeutic effect of the therapeutic compound.
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- Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
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A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
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- Anthracycline glycoside compositions, their use and preparation
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Anthracycline glycoside antibiotics are complexed with cardiolipin and then encapsulated in liposomes to reduce mammalian cardiac tissue uptake of the anthracycline glycoside and to thereby reduce the deleterious effect of such cardiac tissue uptake. The invention is directed to the composition, preparation and use of the encapsulated complex of anthracycline glycoside.
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- Amino acid and dipeptide derivatives of daunorubicin. 1. Synthesis, physicochemical properties, and lysosomal digestion
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The synthesis of amino acid and dipeptide derivatives of daunorubicin (DNR) is described. The binding-affinity parameters for DNA of those derivatives were determined by a spectral titration method. The affinity constants of the amino acid and dipeptide derivatives are, respectively, three and ten times lower than that of DNR. The susceptibility of those derivatives toward lysosomal peptidases was studied. It was found that the Leu and the Ala-Leu derivatives are the most rapidly hydrolyzed into DNR. It is concluded that Leu-DNR and Ala-Leu-DNR could act as prodrugs of DNR, which could be activated inside or in the close vicinity of tumor cells which display a high aminopeptidase activity.
- Masquelier,Baurain,Trouet
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p. 1166 - 1170
(2007/10/02)
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- L-lyxohex-1-enopyranose derivative
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Anthracyclinone glycoside antibiotics including the known antibiotics daunomycin and adriamycin, as well as other, novel glycoside antibiotics of the formula (VIII): STR1 wherein WHEN R1 is hydrogen, R2 and R3 are each independently hydrogen, methyl, methoxy, chloro, or bromo; and when R2 and R3 are hydrogen, R1 is methyl, chloro, or bromo and R4 and R5 are each independently hydrogen or hydroxy are prepared by an acid catalyzed addition reaction between (a) an anthracyclinone compound of the formula STR2 or a dioxolanyl protected derivative thereof (VI) having the formula: STR3 wherein R1, R2, R3, R4 and R5 are as defined above, and R6, R7 and R8 are independently selected from the group consisting of hydrogen and C1 -C4 alkyl; or R7 and R8, together with the carbon atom to which they are bound may form a saturated or unsaturated ring of 3-8 carbon atoms and (b) a novel reactive, protected 1,2-unsaturated pyranoid sugar, preferably, 1,2,3,6-tetradeoxy-3-trifluoroacetamido-4-trifluoroacetoxy-L-lyxo-hex-1-enopyranose which forms protected derivatives of said glycoside antibiotics and then removing the protecting groups from said glycoside antibiotics. These antibiotics are useful in the treatment of various human cancers and leukemia such as sarcomas, breast cancer, bronchogenic carcinoma, malignant lymphomas, neuroblastomas, acute leukemia and bladder cancer.
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- Antibiotic 20,798 R.P.
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The antibiotic 20,798 R.P. of the formula: SPC1 Is of special interest because of its anti-tumor activity. The antibiotic is produced by culture of the microorganism Streptomyces coeruleorubidus (NRRL 3045).
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- Antibiotic 20,798 R.P.
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The antibiotic 20,798 R.P. of the formula: SPC1 Is of special interest because of its anti-tumour activity, being particularly active against acute lymphoblastic and myeloblastic leucaemias. The antibiotic is produced by culture of the microorganism Streptomyces coeruleorubidus (NRRL 3045).
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