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Advisor(s)
Abstract(s)
Inflammation is a complex and tightly regulated process by a cascade of events that involves the production of prostaglandins (PG) by the inducible isoform cyclooxygenase 2 (COX-2) and the production of reactive pro-oxidant species. Conversely, COX-1, which is consistently present in a variety of tissues, has traditionally been categorized as the primary isoform responsible for maintaining the balance of prostaglandin production. Given the adverse effects associated with currently employed antiinflammatory agents, there is an urgent need to develop novel and efficacious compounds capable of regulating the inflammatory cascade. In this sense, a panel of 28 structurally related pyrazoles were evaluated through the inhibition of human COX-2 and ovine COX-1 activity; the ex vivo production of PGE2 in human whole blood; COX-2 expression in human leukocytes; and human leukocytes’ oxidative burst. The results revealed that some of the tested pyrazoles had a significant inhibitory effect on COX- 2 activity. Pyrazoles 4 and 11B (Fig. 1) stood out as the most potent inhibitors. Pyrazole 11B exhibited greater inhibitory activity against COX-2 than COX-1, while pyrazole 14 displayed selective inhibition of COX-1, with an IC50 value lower than 1 μM. Interestingly, pyrazoles 14 and 16 (Fig. 1) downregulated the COX-2 expression in human leukocytes. Several of the tested pyrazoles, namely compound 4, showed a potential suppressive effect (IC50 5 μM) against human leukocytes’ oxidative burst. In addition, various pyrazoles were able to inhibit both COX-2 activity and oxidative burst, particularly the pyrazoles 1B, 4 and 11B.
Description
Keywords
Prostaglandin COX-1
Citation
Silva, J. M., Rocha, S., Silva, V. L. M., Silva, A. M. S., Moreira, F., Fernandes, E., & Freitas, M. (2023). Revealing the immunomodulatory potential of pyrazoles and exploring structure-activity relationships. Em R. P. Rocha & J. L. Faria (Eds.), Livro de Resumos do XXVII Encontro Luso-Galego de Química (p. 272). Sociedade Portuguesa de Química.
Publisher
Sociedade Portuguesa de Química