Characterization in Silico of the Structural Parameters of the Antifungal Agent Ketoconazole

G.A.Araujo, E.P.Silva, R.G.Sanabio, J.A.Pinheiro, M.B. Albuquerque, R.R.Castro, M.M. Marinho, F.K.S.Lima, E.S.Marinho

Abstract: Computational methods of molecular modeling is a useful tool for planning of bioactive compounds such as drugs. This paper aims to describe initial aspects of approach in silico of the antifungal agent ketoconazole, using the ACD / ChemSketch® and Arguslab® software as a necessary step for future studies of structural change, hoping to optimize the action of this drug. The employed methodological steps were: (1) obtaining ketoconazole structure from Chemspide repository; (2) visualization of three-dimensional structure of this drug by ChemSketch® software, with representation of the electron density map; (3) performing semiempirical calculation Arguslab® and Avogrado® software (Austin Model 1-QM-AM1) to optimize the structure, determining the potential electrostatic and Mulliken atomic charges, generation of three- dimensional maps of the electrostatic potential, calculation of orbital border and the minimum potential energy of the molecule. The optimization of ketoconazole structure proved to be feasible. From the electrostatic potential map and load distribution of Mulliken, identified the oxygen atom of the acyl termination (O₃) as a preferred site for nucleophilic reactions. Energy ketoconazole minimum potential was estimated at -139841.4989 kcal/mol The now obtained descriptors will be key objects for future studies of relationships between three-dimensional structure of the drug and its biological activity.

Keywords: ketoconazole, semi-empirical calculation, molecular modeling.

Pages: 133 – 142 | Full PDF Paper