Quantum mechanical and QSAR study of some α-arylpropionic acids as anti-inflammatory agents

The optimal structures of a series of alpha-arylpropionic acids with anti-inflammatory activity are established by using the semi-empirical quantum mechanical procedures, AM1 and AMSOL, in the gas phase and in water solution, respectively. In these calculations, the arylpropionic acids are considered in their neutral and ionized forms. As expected, these compounds exhibit two preferred conformations in which the alpha-hydrogen atoms of the propionic acid group lies approximately in the plane of the central aryl ring. The deprotonation energies are then determined as the difference between the formation energies of the protonated and deprotonated forms. A Quantitative Structure Activity Relationship (QSAR) study reveals that only the gas phase results compare to some extent favorably with the anti-inflammatory activity. As expected, the smaller the deprotonation energy, the larger the anti-inflammatory activity. Satisfactory relationships between the in vivo activities and deprotonation energies, the HOMO energies and lipophilicities were found. (C) Elsevier, Paris.