Improvement of anti-inflammation performance in the form of inclusion complexes of ethyl-(2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carbonyl)glycine with β-cyclodextrin

Abstract

The demand for drugs that are highly soluble, non-toxic, safe, and biocompatible has been steadily increasing, particularly for human use. Despite advances in synthetic chemistry, solubility remains a major challenge for many drug-based organic molecules. One effective solution to this problem is the formation of inclusion complexes (ICs) with cyclodextrins (CDs). In this study, we report the development of an inclusion complex between ethyl-(2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carbonyl)glycine (CyMTGlyAc) and β-cyclodextrin (βCD). Complex formation is confirmed through shifts in absorbance and fluorescence intensities, indicating a 1:1 stoichiometric ratio between the guest and the host. Importantly, the solubility of CyMTGlyAc is significantly enhanced upon complexation with βCD. Proton NMR and ROESY analyses reveal that the phenyl ring of CyMTGlyAc remains outside the βCD cavity, while the amide and ethyl groups are encapsulated within it. Natural Bond Orbital (NBO) calculations further support the complex’s formation, showing two energetically favorable orientations. Cell viability assays demonstrate that the improved solubility of the CyMTGlyAc:βCD complex increases its bioavailability without inducing significant toxicity to normal cells. Additionally, the anti-inflammatory properties of CyMTGlyAc are markedly enhanced in the complexed form, with western blot assays confirming improved delivery and therapeutic efficacy. These findings highlight the potential of CyMTGlyAc:βCD inclusion complexes to not only improve the solubility and stability of bioactive compounds but also enhance their therapeutic performance, making them a promising approach for pharmaceutical applications.