Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective... Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds ( 1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC = 12.98 µM and IC = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC > 50 µM and, COX-2; IC > 50 µM). The 50 50 50 enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity. Keywords 4-Thiazolone · One-pot multicomponent reaction · Anti-inflammatory · Lipoxygenase Introduction inflammatory leukotrienes that regulate inflammation, pain, and fever, as well as some diverse physiological reactions Lipoxygenase (LOX) enzyme produces leukotrienes (LTs) such as blood flow, thrombosis, renal and gastrointestinal and lipoxins (LXs) from arachidonic acid (AA) LT–LX functions (Allaj et al. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemical Papers Springer Journals

Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

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Publisher
Springer International Publishing
Copyright
Copyright © 2018 by Institute of Chemistry, Slovak Academy of Sciences
Subject
Chemistry; Chemistry/Food Science, general; Industrial Chemistry/Chemical Engineering; Biochemistry, general; Medicinal Chemistry; Materials Science, general; Biotechnology
ISSN
0366-6352
eISSN
1336-9075
D.O.I.
10.1007/s11696-018-0520-9
Publisher site
See Article on Publisher Site

Abstract

Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds ( 1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC = 12.98 µM and IC = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC > 50 µM and, COX-2; IC > 50 µM). The 50 50 50 enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity. Keywords 4-Thiazolone · One-pot multicomponent reaction · Anti-inflammatory · Lipoxygenase Introduction inflammatory leukotrienes that regulate inflammation, pain, and fever, as well as some diverse physiological reactions Lipoxygenase (LOX) enzyme produces leukotrienes (LTs) such as blood flow, thrombosis, renal and gastrointestinal and lipoxins (LXs) from arachidonic acid (AA) LT–LX functions (Allaj et al.

Journal

Chemical PapersSpringer Journals

Published: Jun 1, 2018

References

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