Preparation and characterization of a new harmine-based antiproliferative compound in complex with cyclodextrin: Increasing solubility while maintaining biological activity

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Résumé

L-type profile until 80 mM which suggest a 1:1 stoichiometry and a K1:1 of 116 M-1 and a CE of 0.28 have been calculated. This 1:1 stoichiometry was confirmed by Job Plot experiment, following the CD H-3 proton by 1H NMR. Secondly, 1H NMR study of compound 2 in presence of βCD and geometry optimization of the complex has underline an inclusion of 2 into the CD, via the indole part of the drug. Finally, the efficiency of the 2 antiproliferative effect is not affected by the complexation, as shown by viability test.]]>

langueAnglais
Pages135-140
Nombre de pages6
journalEuropean Journal of Pharmaceutical Sciences
Volume77
Les DOIs
étatPublié - 22 juin 2015

Empreinte digitale

Harmine
Cyclodextrins
Solubility
Pharmaceutical Preparations
Protons
Buffers
Glucose
Cell Line
Neoplasms

mots-clés

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    @article{e1dbd568168a473fa162a8d4227d5b33,
    title = "Preparation and characterization of a new harmine-based antiproliferative compound in complex with cyclodextrin: Increasing solubility while maintaining biological activity",
    abstract = "The trisubstituted harmine derivative, 2, present a submicromolar antiproliferative activity on 5 cancer cell lines but a moderate kinetic solubility in pH 7.4 buffer. The aim of this work was to develop a 2-cyclodextrin complex in order to increase the drug solubility while maintaining the biological activity. Firstly, the 2 increasing solubility in presence of several cyclodextrins (CDs) has been shown, with a maximum for 7 glucose subunit CD (βCD and 2HP-βCD). Phase solubility experiment in presence of 2HP-βCD has underline an AL-type profile until 80 mM which suggest a 1:1 stoichiometry and a K1:1 of 116 M-1 and a CE of 0.28 have been calculated. This 1:1 stoichiometry was confirmed by Job Plot experiment, following the CD H-3 proton by 1H NMR. Secondly, 1H NMR study of compound 2 in presence of βCD and geometry optimization of the complex has underline an inclusion of 2 into the CD, via the indole part of the drug. Finally, the efficiency of the 2 antiproliferative effect is not affected by the complexation, as shown by viability test.",
    keywords = "Antiproliferative activity, Complexation, Cyclodextrin, Solubility",
    author = "C{\'e}line Meinguet and Bernard Masereel and Johan Wouters",
    year = "2015",
    month = "6",
    day = "22",
    doi = "10.1016/j.ejps.2015.06.010",
    language = "English",
    volume = "77",
    pages = "135--140",
    journal = "European Journal of Pharmaceutical Sciences",
    issn = "0928-0987",
    publisher = "Elsevier",

    }

    TY - JOUR

    T1 - Preparation and characterization of a new harmine-based antiproliferative compound in complex with cyclodextrin: Increasing solubility while maintaining biological activity

    AU - Meinguet,Céline

    AU - Masereel,Bernard

    AU - Wouters,Johan

    PY - 2015/6/22

    Y1 - 2015/6/22

    N2 - The trisubstituted harmine derivative, 2, present a submicromolar antiproliferative activity on 5 cancer cell lines but a moderate kinetic solubility in pH 7.4 buffer. The aim of this work was to develop a 2-cyclodextrin complex in order to increase the drug solubility while maintaining the biological activity. Firstly, the 2 increasing solubility in presence of several cyclodextrins (CDs) has been shown, with a maximum for 7 glucose subunit CD (βCD and 2HP-βCD). Phase solubility experiment in presence of 2HP-βCD has underline an AL-type profile until 80 mM which suggest a 1:1 stoichiometry and a K1:1 of 116 M-1 and a CE of 0.28 have been calculated. This 1:1 stoichiometry was confirmed by Job Plot experiment, following the CD H-3 proton by 1H NMR. Secondly, 1H NMR study of compound 2 in presence of βCD and geometry optimization of the complex has underline an inclusion of 2 into the CD, via the indole part of the drug. Finally, the efficiency of the 2 antiproliferative effect is not affected by the complexation, as shown by viability test.

    AB - The trisubstituted harmine derivative, 2, present a submicromolar antiproliferative activity on 5 cancer cell lines but a moderate kinetic solubility in pH 7.4 buffer. The aim of this work was to develop a 2-cyclodextrin complex in order to increase the drug solubility while maintaining the biological activity. Firstly, the 2 increasing solubility in presence of several cyclodextrins (CDs) has been shown, with a maximum for 7 glucose subunit CD (βCD and 2HP-βCD). Phase solubility experiment in presence of 2HP-βCD has underline an AL-type profile until 80 mM which suggest a 1:1 stoichiometry and a K1:1 of 116 M-1 and a CE of 0.28 have been calculated. This 1:1 stoichiometry was confirmed by Job Plot experiment, following the CD H-3 proton by 1H NMR. Secondly, 1H NMR study of compound 2 in presence of βCD and geometry optimization of the complex has underline an inclusion of 2 into the CD, via the indole part of the drug. Finally, the efficiency of the 2 antiproliferative effect is not affected by the complexation, as shown by viability test.

    KW - Antiproliferative activity

    KW - Complexation

    KW - Cyclodextrin

    KW - Solubility

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    U2 - 10.1016/j.ejps.2015.06.010

    DO - 10.1016/j.ejps.2015.06.010

    M3 - Article

    VL - 77

    SP - 135

    EP - 140

    JO - European Journal of Pharmaceutical Sciences

    T2 - European Journal of Pharmaceutical Sciences

    JF - European Journal of Pharmaceutical Sciences

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