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 (5a–5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo 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 (IC50 0.05 μM), exhibiting IC50 values in the range of 0.76–9.01 μM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 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 IC50 value of 15.32 μM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 μM, respectively. Standard zileuton exhibited an IC50 value of 11.00 μM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e 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.

中文翻译：

---

用于治疗镇痛和炎症的 4-(4-氯噻吩-2-基)噻唑-2-胺衍生物的修饰：合成以及体外、体内和计算机研究


炎症是对多种传染源的保护性反应。为了开发一种新的抗炎药物，我们在本研究中探索了一种具有药理学重要意义的噻唑支架。通过多步合成方法，我们合成了七种新的噻唑衍生物（5a-5g）。最初，我们检查了体外使用 COX-1、COX-2 和 5-LOX 酶测定我们的化合物的抗炎潜力。后体外确认，潜在的化合物受到体内镇痛和抗炎研究。采用热板法进行镇痛，并检测角叉菜胶引起的炎症。总体而言，与塞来昔布（IC 50 0.05 μM)，展示 IC 50值范围为 0.76–9.01 μM。化合物 5b、5d 和 5e 是具有最低 IC 值的主要选择性 COX-2 抑制剂50值和选择性指数 (SI) 值分别为 42、112 和 124。同样，在 COX-1 测定中，我们的化合物的效力相对较低，但仍然令人鼓舞。标准阿司匹林表现出 IC 50值为 15.32 μM。在 5-LOX 结果中，化合物 5d 和 5e 再次在 IC 中占主导地位50值分别为 23.08 和 38.46 μM。标准齐留通展出IC 50值为 11.00 μM。根据 COX/LOX 和 SI 效力，对化合物 5d 和 5e 进行了体内镇痛和抗炎研究。浓度为5、10和20mg/kg体重的化合物5d和5e在动物模型中具有显着性。 此外，我们还探讨了化合物 5d 和 5e 在各种炎剂中的潜在作用。类似地，化合物 5d 和 5e 在抗伤害性测定中也具有显着效力。这两种化合物与COX和LOX靶蛋白的分子对接相互作用进一步增强了它们在COX/LOX通路抑制中的应用潜力。