New imidazolone derivatives comprising a benzoate or sulfonamide moiety as anti-inflammatory and antibacterial inhibitors: Design, synthesis, selective COX-2, DHFR and molecular-modeling study.

Autor: Metwally NH; Chemistry Department, Faculty of Science, Cairo University, Egypt. Electronic address: nhmmohamed@yahoo.com., Mohamed MS; Chemistry Department, Faculty of Science, Cairo University, Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Jun; Vol. 99, pp. 103438. Date of Electronic Publication: 2019 Nov 13.
DOI: 10.1016/j.bioorg.2019.103438
Abstrakt: New imidazol-5-one derivatives 12a,b and 12e, f, 14a,b and 16a,b were synthesized and screened for their in vivo anti-inflammatory activity using a standard acute carrageenan-induced rat paw oedema method. All the tested compounds exhibited good anti-inflammatory activity; especially compound 12f which produced the maximum effect of 49.0% compared to the standard drug, celecoxib, (43.1%). The most active anti-inflammatory agents 12a, 12e, and 12f were studied for their interactions with enzyme COX-2 compared to celecoxib. The study showed that, compound 12e exhibited a high selectivity towards COX-2 inhibition with IC 50  = 0.087 μM. Moreover, the antibacterial screening indicated that some synthesized compounds showed good antibacterial activity toward the Gram-negative bacteria Escherichia coli. Additionally, compounds 7, 12a, 12f, and 12 showed a good binding affinity with enzyme dihydrofolate reductase (DHFR) whereas compound 12f has a higher inhibitory effect on DHFR than the tested compounds 7, 12a and 12 h. On the other hand, the combination between these tested compounds and sulfadiazine as a reference drug (10 μM compound + 1 μM reference), showed that compound 12 h has higher potency (0.078 ± 0.002) than sulfadiazine (0.135 ± 0.004). In addition, docking analysis was performed and it confirmed the presented results.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2019. Published by Elsevier Inc.)
Databáze: MEDLINE
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