Анотація
Background: Gedunin, a limonoid, is linked with antimalarial, anticancer and anti-allergic activities. This study was aimed at preparing an inclusion complex of gedunin and 2-hydroxypropyl-β-cyclodextrin (HBD) to increase solubility of gedunin in polar solvents which will increase absorption and bioavailability in vivo and thus enhance pharmacological effects.
Materials and methods: Gedunin was obtained from the hexane extract of Entandrophragma angolense heartwood by column and preparative thin layer chromatography. The structure was previously confirmed by spectroscopic means (NMR). The electronic absorption spectra data of the complexes formed between gedunin and HBD in various solvents was determined using the UV-VIS spectrophotometer. The stoichiometry of inclusion was determined by Job’s method of continuous variation.
Results: Evidence of interaction was observed between gedunin and HBD in the various solvents but gedunin and its complex with HBD exhibited sharp absorption bands in acetate buffer (pH 3.5). The spectrophotometric titrations showed curves with a single point of inflexion when the experiment was carried out at 250C (298 K) and 370C (310 K). A stoichiometric ratio of 1:1 for complex
formation was obtained. The formation constants (Kf ) obtained at 250C and 37 0C were 9.539 x 103 M-1 and 1.853 x 104 M-1 respectively. Thermodynamic considerations revealed hydrophobic interaction between gedunin and HBD.
Conclusion: A stable inclusion complex of gedunin and HBD was formed at room and body temperature. This complex formation involved trapping of poorly soluble gedunin into the hydrophobic core of the cyclodextrin and may enhance the pharmacological activity of gedunin in vivo.
Keywords: Gedunin, 2-hydroxypropyl-β-cyclodextrin, Inclusion complexes, Spectrophotometry, Thermodynamic considerations
Résumé
Contexte: Le gédunin, un limonoïde, est liée aux activités antipaludiques, anticancéreuses et antiallergiques. Cette étude avait pour but de préparer un complexe d’inclusion de gédunin et de 2-hydroxypropyl-β-cyclo-dextrine (HBD) pour augmenter la solubilité dugédunin dans des solvants polaires qui augmentent l’absorption et la biodisponibilité in vivo et par conséquence d’améliorer les effets pharmacologiques.
Matériels et méthodes: Le gédunin a été obtenu à partir de l’extrait d’hexane d’Entandrophragmaangolense duramen par colonne etpréparation en couche mince de la Chromatographie. La structure était confirmée préalablement par des moyens spectroscopiques (RMN). Les données des spectres d’absorption électroniques des complexes formés entre le gédunin et HBD dans différents solvants ont été déterminées en utilisant le spectrophotomètre UV-VIS. La stœchiométrie d’inclusion a été déterminée par la méthode de Job de variation continuée.
Résultats: Preuve d’interaction a été observée entre le gédunin et HBD dans les différents solvants, mais le gédunin et son complexe avec HBD présentait des bandes d’absorption nettes dans un tampon d’acétate (pH 3,5). Les titrages spectrophotométries ont montré des courbes avec un point d’inflexion unique lorsque l’expérience a été effectuée à 250C (298 K) et 370C (310 K). Un rapport stœchiométrique de1: 1 pour la formation du complexe a été obtenu. Les constantes de formation (Kf ) obtenus à 250Cet 37 0C étaient 9,539 x103 M-1et 1,853 x 104 M-1respectivement. Les considérations thermodynamiques ont révélé une interaction hydrophobique entre le gédunin et HBD.
Conclusion: Un complexe d’inclusion stable de gédunin et HBD a été formé à la températurede salle et du corps. Cette formation de complexe a impliqué le piégeage des gédunins peu soluble dans le noyau hydrophobiqu e de la cyclo-dextrine et peut augmenter l’activité pharmacologique de gédunin in vivo.
Mots-clés: Gédunin, 2-hydroxypropyl-β-cyclo-dextrine, Complexes d’inclusion, Spectrophotométrie, Considérations thermodynamiques Presented as oral presentation at the 4th Unibadan Conference of Biomedical Research, July 1 -4, 2014, Faculty of Basic Medical Science, College of Medicine, University of Ibadan.
Correspondence: Prof. A.O. Adegoke, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Nigeria. E-mail: ao.adegoke@mail.ui.edu.ng; jireade@yahoo.com
Посилання
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