Binding of anti-inflammatory drug indomethacin with cyclodextrin and DNA: solubility, spectroscopic, and voltammetric studies

Shehatta, I S; Ibrahim, M S
October 2001
Canadian Journal of Chemistry;Oct2001, Vol. 79 Issue 10, p1431
Academic Journal
The interaction of the anti-inflammatory drug indomethacin (IMC) with α-, β-cyclodextrins (CDs) and calf thymus deoxyribonucleic acid (ct-DNA) have been investigated in the Britton-Robinson (BR) buffer (pH = 7.2) using solubility, spectroscopic, and voltammetric methods. The measurements show that the IMC molecule, acting as an intercalator, is inserted, from the p-chlorobenzoyl part, into the cavity of the cyclodextrins as well as into the base-stacking domain of the ct-DNA double helix. Upon addition of β-CD in a buffered IMC solution, the solubility of IMC increases and the Gibbs free energies of transfer of the drug from aqueous solution to the cavity of β-CD are negative and increase negatively with increasing β-CD concentration. The interaction of IMC with CDs and ct-DNA causes hypochromism and bathochromic shifts in the absorption spectra, along with pronounced changes in the electrochemical behaviour of the drug. The stoichiometry of complexes formed in solution is inferred to be 1:1. The binding constants were calculated from the increase of the solubility, the strong hypochromism, and the decrease in peak current of IMC upon the addition of the host molecules. IMC has a higher affinity for β-CD than for α-CD, as the IMC–β-CD interaction is the most exergonic. Binding is interpreted in terms of the intercalative (hydrophobic) interactions with the ct-DNA helix (i.e., the stacked base pairs) or within CD cavity.Key words: cyclodextrin, ct-DNA, anti-inflammatory drug, indomethacin, binding constant, solubility, spectra, voltammetry.Faisant appel à des méthodes basées sur la solubilité, la spectroscopie et la voltampérométrie et opérant dans un tampon de Britton-Robinson (BR) (pH = 7,2), on a étudié l'interaction entre l'indométhacine (IMC), un antiinflammatoire, et les α- et β-cyclodextrines (CD) et l'acide désoxyribonucléique de la thyroïde du veau (ct-DNA). Les mesures montrent que la molécule d'IMC s'intercale, à partir de la portion p-chlorobenzoyle, dans la cavité des cyclodextrines ainsi que dans le domaine d'empilement des bases de la double hélice du ct-DNA. Par addition de β-CD dans une solution tamponnée d'IMC, la solubilité de l'IMC augmente; les énergies libres de Gibbs du transfert du médicament à partir de la solution aqueuse vers la cavité de la β-CD sont négatives et elles augmentent de façon négative avec une augmentation de la concentration de β-CD. L'interaction de l'IMC avec les CD et le ct-DNA provoque une hypochromie et une bathochromie dans les spectres d'absorption et des changements importants dans le comportement électrochimique du médicament. On fait l'hypothèse que la stoechiométrie des complexes qui se forment en solution est 1:1. Les constantes de fixation ont été calculées à partir de l'augmentation de la solubilité, la forte hypochromie et la diminution du courant de sommet de l'IMC lors de l'addition de molécules hôtes. L'affinité de l'IMC est plus grande pour la β-CD que pour la α-CD parce que l'interaction IMC–β-CD est la plus exergonique. La fixation est interprétée en termes de la facilité des interactions d'intercalation (hydrophobes) dans l'hélice de la ct-DNA (c'est-à-dire les paires de bases empilées) ou à l'intérieur de la cavité de la CD.Mots clés : cyclodextrine, ct-DNA, médicament antiinflammatoire, indométhacine, constante de fixation, solubilité, spectres, voltampérométrie.[Traduit par la Rédaction]


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