一种新合成的 1,2,4-三唑衍生物的抗炎、镇痛和解热活性的体内评价。
An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1, 2, 4 Triazole derivatives.
机构信息
Department of Pharmacy, Iqra University Islamabad Campus, Islamabad, Pakistan.
Department of Pharmacy, Abasyn University Islamabad Campus, Islamabad, Pakistan.
出版信息
BMC Complement Med Ther. 2021 Dec 31;21(1):304. doi: 10.1186/s12906-021-03485-x.
BACKGROUND
In recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives.
METHODS
Swiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia.
RESULTS
Both of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol [3] was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol [5e] showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice.
CONCLUSIONS
It is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities.
背景
近年来，1,2,4-三唑及其衍生物已被报道具有重要的药理活性。它们具有镇痛、抗结核、抗炎、抗惊厥、抗氧化、抗真菌、抗癌、抗焦虑和抗抑郁作用。本研究旨在评估三唑衍生物的潜在抗炎、镇痛和退热活性。
方法
本研究使用体重为 20-30g（雌性 10-24 周，雄性 5-14 周）的瑞士白化雄性和雌性小鼠和体重为 200-300g（8-10 周龄）的 Wister Kyoto 雄性和雌性大鼠。使用角叉菜胶（λ）和卵白蛋白诱导的足肿胀模型来检测抗炎活性。通过乙酸和甲醛诱导的扭体反应来评估镇痛作用，此外，通过酵母诱导的发热来评估退热活性。
结果
与标准药物布洛芬相比，两种测试化合物均表现出令人鼓舞的抗炎、镇痛和退热效果。化合物（S）-1-（4-氨基-5-巯基-4H-1,2,4-三唑-3-基）乙醇[3]的最大抑制水肿率为（91）%，而参考药物布洛芬（82）%，而（S）-1-（6-苯基-7H-[1,2,4]三唑并[3,4-b][1,3,4]噻二嗪-3-基）乙醇[5e]与布洛芬（81）%表现出等效结果。这些衍生物还通过乙酸扭体和尾巴浸入试验进行了抗伤害作用筛选。化合物 3 显示出明显的扭体减少（83）%，与标准药物布洛芬的 71.5%相比，而[5]显示出与布洛芬相当的结果，在相同剂量下，扭体减少了 70%，此外，在给小鼠高剂量测试化合物后没有观察到毒性迹象。
结论
从结果来看，化合物 3（化合物 A）和 5（化合物 B）是具有抗炎、镇痛和退热潜力的候选药物，该支架可用于进一步的结构修饰。进一步的研究将有助于评估它们在这些有益活性方面的分子作用机制。
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