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

作者：Shehatta IS^*; Ibrahim MS

来源：Canadian Journal of Chemistry, 2001, 79(10): 1431-1438.

DOI：10.1139/cjc-79-10-1431

• cyclodextrin
• ct-DNA
• anti-inflammatory drug
• indomethacin
• binding constant
• solubility
• spectra
• voltammetry

The interaction of the anti-inflammatory drug indomethacin (IMC) with alpha-, beta -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 beta -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 beta -CD are negative and increase negatively with increasing beta -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 beta -CD than for alpha -CD, as the IMC-beta -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.

• 出版日期2001-10