Theoretical study on the structure and reactive sites of three non-steroidal anti-inflammatory drugs: Ibuprofen, Naproxen and Tolmetin acids

NORA OKULIK , ALICIA H. JUBERT

JOURNAL OF MOLECULAR STRUCTURE THEOCHEM

Elsevier

Año: 2006 p. 135 - 141

0166-1280

The mode of action of the non-steroid anti-inflammatory drugs (NSAIDs) is attributed primarily to the inhibition of prostaglandin (PG) synthesis, and more specifically, to the inhibition of the COX enzyme system. In an effort to gain a deeper insight on the properties of NSAIDs as ibuprofen , naproxen and tolmetin, that will provide knowledge of their action, we have performed theoretical studies in the frame of the AIM Bader´s theory (atoms in molecules). Through the analysis of the topological properties of the three molecules it was shown that the C-C, C-N, N-H and C-H ring bonds as well as the CaO and O?H bonds of the carboxylic groups are strong shared interactions. A hydrogen bond is localized in the tolmetin acid between O16?H31 as was anticipated in the analysis of its MEP.a-methyl-2-naphthalene acetic acid] and tolmetin [1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid], that will provide knowledge of their action, we have performed theoretical studies in the frame of the AIM Bader?s theory (atoms in molecules). Through the analysis of the topological properties of the three molecules it was shown that the C?C, C?N, N?H and C?H ring bonds as well as the CaO and O?H bonds of the carboxylic groups are strong shared interactions. A hydrogen bond is localized in the tolmetin acid between O16?H31 as was anticipated in the analysis of its MEP. The analysis of the sites of major concentration electronic charge performed through the electrostatic potential maps and the calculation of the non bonding critical points shown that the oxygen atoms of the NSAIDs would be the preferential sites for the electrophilic attack, among them those corresponding to the carboxylic groups.