- Improved therapeutic efficacy of doxorubicin through conjugation with a novel peptide drug delivery technology (Vectocell)
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Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attractive candidates to minimize many of the limitations observed for a broad range of cytotoxic molecules. The studies reported here characterized the in vitro and in vivo efficacy of a range of Vectocell peptides conjugated to doxorubicin through different linkers. These studies show that the in vivo therapeutic index of doxorubicin can be improved by conjugation with a specific Vectocell peptide (DPV 1047) through an ester linker to C14 of doxorubicin, in both colon and breast tumor models. This conjugate was also shown to have significant in vivo antitumoral activity in a model resistant to doxorubicin, suggesting that this conjugate is able to circumvent the multidrug resistance (MDR) phenotype. These experiments therefore provide support for the use of the Vectocell technology with other cytotoxic agents.
- Meyer-Losic, Florence,Quinonero, Jér?me,Dubois, Vincent,Alluis, Bertrand,Dechambre, Mireille,Michel, Matthieu,Cailler, Fran?oise,Fernandez, Anne-Marie,Trouet, André,Kearsey, Jonathan
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- Synthetic method for valrubicin
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The invention discloses a synthetic method for valrubicin. The synthetic method comprises the following steps: subjecting daunorubicin hydrochloride to a bromination reaction, with the carbonyl groupof the daunorubicin hydrochloride being under the protection of triethyl orthoformate, subjecting an obtained reaction solution to concentration treatment, then directly subjecting a concentrated solution to a deprotection reaction, carrying out salt-induced precipitation after completion of the deprotection reaction so as to crystallize a bromide intermediate, allowing the crystallized bromide intermediate to react with potassium n-pentanoate, and carrying out a reaction with trifluoroacetic anhydride to form an amide so as to prepare valrubicin. The synthetic method provided by the inventionhas the advantages of mild reaction conditions, short reaction time, easiness in operation and control, and applicability to large-scale industrial production.
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Paragraph 0018
(2018/09/21)
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- Synthesis and antitumor activity of new D-galactose-containing derivatives of doxorubicin
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A general scheme of synthesis of antibiotic doxorubicin derivatives is based on the 13-dimethyl ketal of 14-bromodaunorubicin (4). The interaction of 4 with melibiose (5), lactose (6), 3-methoxy-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-4- oxybenz
- Olsufyeva, Eugenia N.,Tevyashova, Anna N.,Trestchalin, Ivan D.,Preobrazhenskaya, Maria N.,Platt, David,Klyosov, Anatole
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p. 1359 - 1367
(2007/10/03)
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