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3-羟基吡啶-4-酮新衍生物的抗炎作用研究

A study on the anti-inflammatory effects of new derivatives of 3-hydroxy pyridine-4-one.

作者信息

Hajhashemi Valiollah, Mojiri-Froshani Hoda, Saghaei Lotfollah, Fassihi Afshin

机构信息

Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Adv Biomed Res. 2014 May 28;3:134. doi: 10.4103/2277-9175.133276. eCollection 2014.

Abstract

BACKGROUND

Derivatives of pyridine-4-one act as iron chelators and possess various pharmacological effects such as antifungal, antimalarial, antiviral, anti-inflammatory, and analgesic effects. The aim of our study was to evaluate the anti-inflammatory effects of the three new derivatives of pyridine-4-one.

MATERIALS AND METHODS

Carrageenan-induced paw edema in rats and croton oil-induced ear edema in mice were used to evaluate the anti-inflammatry effects of three 3-hydroxy-pyridine-4-one derivatives (compounds A, B, and C). Compound A (10, 20 mg/kg), compound B (200, 400 mg/kg), and compound C (100, 200 mg/kg), vehicle (1 mL/kg), and indomethacin as standard drug (10 mg/kg) were injected intraperitoneally 30 min prior to carrageenan injection and 4 h later, the paw volume was measured using a mercury plethysmograph. The maximum dose of each test compound was used in the croton oil-induced ear edema test.

RESULTS

All compounds showed significant anti-inflammatory activity in both tests. On a molar basis, compound A had the greatest potency, which may be due to the presence of a benzyl group substitution on the pyridine ring.

CONCLUSIONS

Because cyclooxygenase and lipoxygenase as key enzymes of the inflammation pathway are heme-dependent, it seems that the anti-inflammatory effect of derivatives of pyridine-4-one may be related to their iron chelating properties. However, more investigations are needed to find out their exact mechanism of actions.

摘要

背景

吡啶 - 4 - 酮衍生物可作为铁螯合剂,并具有多种药理作用,如抗真菌、抗疟疾、抗病毒、抗炎和镇痛作用。我们研究的目的是评估三种新型吡啶 - 4 - 酮衍生物的抗炎作用。

材料与方法

采用角叉菜胶诱导的大鼠足爪水肿和巴豆油诱导的小鼠耳水肿来评估三种3 - 羟基 - 吡啶 - 4 - 酮衍生物(化合物A、B和C)的抗炎作用。在注射角叉菜胶前30分钟腹腔注射化合物A(10、20毫克/千克)、化合物B(200、400毫克/千克)、化合物C(100、200毫克/千克)、赋形剂(1毫升/千克)以及作为标准药物的吲哚美辛(10毫克/千克),4小时后,使用水银体积描记器测量足爪体积。在巴豆油诱导的耳水肿试验中使用每种受试化合物的最大剂量。

结果

在两项试验中,所有化合物均显示出显著的抗炎活性。以摩尔为基础,化合物A的效力最大,这可能是由于吡啶环上存在苄基取代。

结论

由于环氧合酶和脂氧合酶作为炎症途径的关键酶是血红素依赖性的,吡啶 - 4 - 酮衍生物的抗炎作用似乎可能与其铁螯合特性有关。然而,需要更多的研究来查明它们的确切作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d386/4063108/73ae4a9c7ade/ABR-3-134-g001.jpg

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