The aim of this study was to investigate the anti-inflammatory effects of two new isoxazoline-acylhydrazone derivatives: N′-(4-methoxybenzylidene)-6-(4-nitro-benzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-123) and N′-(4-chlorobenzylidene)-6-(4-chlorobenzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-99). An air pouch induced by carrageenan was used for screening the best dose of R-99 and R-123. Using this mouse model, leukocyte migration and cytokine levels (TNF-α and IL-1β) were determined. Paw edema induced by several phlogistic agents and vascular permeability induced by acetic acid were employed to investigate the mechanism of action of the isoxazoline-acylhydrazone derivatives. A docking study was performed with the human histamine H1 receptor to investigate potential antihistaminic activity. Treatment with the compounds reduced leukocyte migration in the air pouch at all doses tested. TNF-α and IL-1β levels were similarly reduced by the two compounds. Vasoactive amines were inhibited in models of paw edema induced by several agents and vascular permeability induced by acetic acid. The docking study suggests that R-99 and R-123 may be inhibitors of the histamine H1 receptor. In conclusion, the results indicate that R-99 and R-123 exhibit promising anti-inflammatory activity related to their ability to inhibit TNF-α, IL-1β, and vasoactive amine production, as well as reduce leukocyte migration and inhibit mast cell degranulation.

中文翻译：

---

新型氮杂双环异恶唑啉酰基腙衍生物的抗炎活性评价及分子对接研究。

本研究的目的是研究两种新的异恶唑啉-酰基腙衍生物的抗炎作用：N '-(4-methoxybenzylidene)-6-(4-nitro-benzoyl)-3 a ,5,6,6 a - tetrahydro-4 H -pyrrolo[3,2 - d ]isoxazole-3-carbohydrazide (R-123) 和N '-(4-chlorobenzylidene)-6-(4-chlorobenzoyl)-3 a ,5,6,6 a -四氢-4 H -吡咯并[3,2- d]isoxazole-3-carbohydrazide (R-99)。卡拉胶诱导的气囊用于筛选R-99和R-123的最佳剂量。使用该小鼠模型，测定了白细胞迁移和细胞因子水平（TNF-α 和 IL-1β）。几种燃素引起的爪水肿和乙酸引起的血管通透性被用来研究异恶唑啉-酰基腙衍生物的作用机制。对人类组胺 H1 受体进行了一项对接研究，以研究潜在的抗组胺活性。在所有测试剂量下，用化合物处理减少了气囊中的白细胞迁移。两种化合物同样降低了 TNF-α 和 IL-1β 水平。在几种药剂诱导的爪水肿模型和乙酸诱导的血管通透性模型中，血管活性胺受到抑制。对接研究表明，R-99 和 R-123 可能是组胺 H1 受体的抑制剂。总之，结果表明，R-99 和 R-123 表现出有希望的抗炎活性，这与它们抑制 TNF-α、IL-1β 和血管活性胺产生的能力有关，以及减少白细胞迁移和抑制肥大细胞脱粒的能力。 .