Pyrazolone-type compounds (part II): in vitro and in silico evaluation of antioxidant potential; structure-activity relationship

• Published in: RSC advances Vol. 13; no. 5; pp. 2884 - 2895
• Main Authors: Branković, Jovica, Milovanović, Vesna M, Petrović, Zorica D, Simijonović, Dušica, Petrović, Vladimir P
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 18-01-2023; The Royal Society of Chemistry
• Subjects: Antioxidants; Catechol; Chemistry; Density functional theory; Enthalpy; Pyrazolones; Scavenging; Solvents
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d2ra08280b

The pyrazolone class comprises a variety of hybrid compounds displaying diverse biological actions. Although studied for decades, these compounds are still of interest due to their facile chemical transformations. In our previous work, we presented the synthetic route of functionalised pyrazolone derivatives. The presence of pyrazolone structural motif in many drugs, such as edaravone, prompted us to investigate the antioxidant features of the selected compounds. In this paper, we provide an extensive
and
description of the antioxidant properties of selected pyrazolone analogues. The obtained
results revealed their great antiradical potency against the DPPH radical (IC
values in the 2.6-7.8 μM range), where the best results were obtained for analogues bearing a catechol moiety. Density functional theory (DFT) was used to assess their antioxidant capacity from the thermodynamic aspect. Here, good agreement with
results was achieved. DFT was employed for the prediction of the most preferable radical scavenging pathway, also. In polar solvents, the SPLET mechanism is a favourable scavenging route, whereas in nonpolar solvents the HAT is slightly predominant. Furthermore, antioxidant mechanisms were studied in the presence of relevant reactive oxygen species. The obtained values of the reaction enthalpies with the selected radicals revealed that HAT is slightly prevailing in polar solvents, while the SPLET mechanism is dominant in nonpolar solvents. Regarding the well-known antioxidant features of the drug edaravone, these findings represent valuable data for this pyrazolone class and could be used as the basis for further investigations.