Evaluation of molecular inclusion of azole antifungals by β-cyclodextrin using computational molecular approach

Abstract Azole antifungals are frequently used to treat fungal infections in humans. The two biggest problems with these azoles are the development of antifungal drug resistance and their poor water solubility, which makes them challenging to administer. One method to get around the limitations of azole delivery is inclusion complex development. Using molecular docking and Density Functional Theory (DFT) with PM3 calculations, we evaluated the chemical stability and reactivity of azole antifungals, including fluconazole, ketoconazole, miconazole, clotrimazole, and propiconazole, with β-cyclodextrin. Molecular docking was used to describe many medicinal molecule binding positions in beta cyclodextrin. Our findings indicate that the most stable inclusion complex is the fluconazole-β-cyclodextrin complex.