Molecular orbital theory applied to the study of nonsteroidal anti-inflammatory drug efficiency

Using a simple quantum mechanical method, we calculated the energy of the h ighest-occupied molecular orbital (E-HOMO) of three groups of anti-inflamma tory compounds, and we have found correlations between E-HOMO of these mole cules and experimental data previously reported on (1) inhibition of sheep- vesicular-gland prostaglandin cyclooxygenase by phenolic compounds, (2) inh ibition of prostaglandin cyclooxygenase in mouse macrophages by salicylates , benzoates and phenols, and (3) peroxyl-radical scavenging and radioprotec tion of a bacterial virus by NSAID drugs, including metiazinic acid, sulind ac, D-penicillamine, piroxicam, indomethacin, benoxaprofen, and aspirin. Ou r correlations using a systematic evaluation of the HOMO energies can be of predictive value in the search for new anti-inflammatory drugs as well as for new radioprotectors. (C) 1999 Elsevier Science Inc.