THEORETICAL-STUDIES ON NONSTEROIDAL ANTIINFLAMMATORY DRUGS - BENOXAPROFEN, CHLORPROMAZINE, AND PIROXICAM

We report quantum chemical semi-empirical calculations of the geometri es and the electronic structures (at AM1 and INDO/S levels) of three n onsteroidal antiinflammatory drugs (NSAIDs), namely, benoxaprofen, chl orpromazine and piroxicam, and a piroxicam metabolite, that have undes irable phototoxic effects. Our calculated electronic spectra in gas ph ase and in water fit reasonably well the observed spectral data. The w avelength of the absorption maxima are not significantly affected by c hanging from gas phase to water (at the SCRF level). We were able to a ssign the observed bands to the calculated transitions. We found also that the spectrum of the piroxicam metabolite actually responsible for the phototoxicity cannot be understood on the sole basis of one of th e tautomers. We hope that these finding will be useful for the underst anding of the photochemical events that lead ultimately to the biologi cal effects. (C) 1995 John Wiley & Sons, Inc.