Reactivity of Biologically Important NSAID Compounds with Superoxide (O2.−), nitric oxide (.NO) and Cyclooxygenase Inhibition

Autor: P. Puig-Parellada, Ramon Pouplana, Carmen Pérez, Juan Sebastián Vera Sánchez, Federico Mármol
Rok vydání: 2007
Předmět:
Zdroj: QSAR & Combinatorial Science. 26:368-377
ISSN: 1611-0218
1611-020X
DOI: 10.1002/qsar.200630067
Popis: In the present study, we investigated the free radical-scavenging effects of eight Nonsteroidal Anti-Inflammatory Drugs (NSAID) using a Superoxide (O2.−) and Nitric Oxide (.NO) generating system in vitro. Indomethacine showed higher scavenging activity against O2.−, it being more potent than ibuprofen and nimesulide at the same concentration. Diclofenac showed a more relevant effect on the .NO scavenging activity than against O2.−. Comparison of the activities of eight compounds showed that the aryl-acetic compounds have higher scavenging activities than the diarylheterocyclic ones. We have also found that the O2 scavenging activity correlates with the Next-Highest-Occupied π-Orbital (NHOMO) levels and the Next-Lowest-Unoccupied π-Orbital (NLUMO)-NHOMO gaps correlate with Cyclooxygenase-1 (COX-1) inhibitory activity. These results suggest that both NHOMO and NHOMO-NLUMO gap energies can be of predictive value in the search for new candidate anti-inflammatory drugs.
Databáze: OpenAIRE