Novel Synthesized Benzophenone Thiazole Hybrids Exhibited Ex Vivo and In Silico Anti-Inflammatory Activity.

Autor: Leão LPMO; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., Neto AK; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., de Jesus Nicácio K; Department of Chemistry, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil., Lavorato SN; Center of Biological Sciences and Health, Federal University of Western Bahia, Barreiras, Bahia, Brazil., Leite FB; Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil., Teixeira KC; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., Murgu M; Waters Corporation, São Paulo, Brazil., de Paula ACC; Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil., Soares MG; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., Chagas-Paula DA; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., Dias DF; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2024 Oct; Vol. 104 (4), pp. e14634.
DOI: 10.1111/cbdd.14634
Abstrakt: Novel benzophenone-thiazole hybrids with different substituents were synthesized and evaluated for anti-inflammatory activity using an ex vivo human whole-blood assay. All hybrids (3c and 5a-h) showed significant anti-inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes. This study provides the first evidence that benzophenone-thiazole hybrids may also dock in mPGES-1, a new attractive anti-inflammatory drug target, besides providing promising ex vivo anti-inflammatory activity. Thus, the novel hybrids are promising anti-inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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