1. Novel Synthesized Benzophenone Thiazole Hybrids Exhibited Ex Vivo and In Silico Anti-Inflammatory Activity.
- Author
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Leão LPMO, Neto AK, de Jesus Nicácio K, Lavorato SN, Leite FB, Teixeira KC, Murgu M, de Paula ACC, Soares MG, Chagas-Paula DA, and Dias DF
- Subjects
- Humans, Catalytic Domain, Structure-Activity Relationship, Benzophenones chemistry, Benzophenones pharmacology, Benzophenones chemical synthesis, Molecular Docking Simulation, Prostaglandin-E Synthases antagonists & inhibitors, Prostaglandin-E Synthases metabolism, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents chemical synthesis, Dinoprostone metabolism, Dinoprostone antagonists & inhibitors, Cyclooxygenase 2 metabolism, Thiazoles chemistry, Thiazoles pharmacology
- Abstract
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.)
- Published
- 2024
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