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Papers of the Week

Papers: 16 Mar 2024 - 22 Mar 2024


Front Pharmacol



Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies.


Mahnashi MH, Rashid U, Almasoudi HH, Nahari MH, Ahmad I, Binshaya AS, Abdulaziz O, Alsuwat MA, Jan MS, Sadiq A


Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (-). Initially, we examined the anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After confirmation, the potential compounds were subjected to analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC 0.05 μM), exhibiting IC values in the range of 0.76-9.01 μM .Compounds , , and were dominant and selective COX-2 inhibitors with the lowest IC values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC value of 15.32 μM. In the 5-LOX results, once again, compounds and were dominant with IC values of 23.08 and 38.46 μM, respectively. Standard zileuton exhibited an IC value of 11.00 μM. Based on the COX/LOX and SI potencies, the compounds and were subjected to analgesic and anti-inflammatory studies. Compounds and at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds and in various phlogistic agents. Similarly, both compounds and were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.