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RMD86是一种噻吩衍生物,可增强小鼠的抗伤害感受和退热活性。

RMD86, a thiophene derivative, promotes antinociceptive and antipyretic activities in mice.

作者信息

da Cruz Ryldene Marques Duarte, Braga Renan Marinho, de Andrade Humberto Hugo Nunes, Monteiro Álefe Brito, Luna Isadora Silva, da Cruz Rayssa Marques Duarte, Scotti Marcus Tullius, Mendonça-Junior Francisco Jaime Bezerra, de Almeida Reinaldo Nóbrega

机构信息

Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil.

Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB 58071-160, Brazil.

出版信息

Heliyon. 2020 Nov 23;6(11):e05520. doi: 10.1016/j.heliyon.2020.e05520. eCollection 2020 Nov.

Abstract

Treatment of pain and fever remains an important challenge for modern medicine. Non-steroidal anti-inflammatory drugs (NSAIDs) are the pharmacological options most often used, but their frequent use exposes the patient to serious side effects and dangerous drug interactions. In this context, thiophene derivatives are promising therapeutic alternatives. In this study, we evaluated the and antinociceptive and antipyretic properties of , a thiophene derivative. At 100 mg/kg, induced no significant changes in the motor coordination of mice in the Rotarod test. At 25, 50, and 100 mg/kg significantly reduced the number of abdominal contortions induced by acetic acid (antinociceptive activity) in mice when compared to the control. In the formalin test, for the first phase, there was a reduction in licking times at doses of 50 and 100 mg/kg. In the second phase, reduction occurred at all doses. In the hot plate test, (at 100 mg/kg) increased latency time in the first 30 min. For antipyretic activity, when compared to the reference drug acetaminophen (250 mg/kg), significantly reduced pyrexia at 30, 60, and 120 min, at dosages of 25, 50 and 100 mg/kg. Molecular docking studies revealed that presents a greater number of interactions and lower energy values than both the co-crystallized ligand and the reference drug (meloxicam) against COX-1 and COX-2 isoenzymes. The results give evidence of the analgesic and antipyretic properties like NSAIDs suggesting its potential for pain therapy.

摘要

疼痛和发热的治疗仍然是现代医学面临的一项重大挑战。非甾体抗炎药(NSAIDs)是最常使用的药物选择,但其频繁使用会使患者面临严重的副作用和危险的药物相互作用。在此背景下,噻吩衍生物是很有前景的治疗替代物。在本研究中,我们评估了一种噻吩衍生物[具体名称未给出]的镇痛和解热特性。在100mg/kg剂量下,[具体名称未给出]在转棒试验中未引起小鼠运动协调性的显著变化。与对照组相比,在25、50和100mg/kg剂量下,[具体名称未给出]显著减少了小鼠由乙酸诱导的腹部扭体次数(镇痛活性)。在福尔马林试验中,在第一阶段,50和100mg/kg剂量下舔舐时间减少。在第二阶段,所有剂量下均出现减少。在热板试验中,[具体名称未给出](100mg/kg)在最初30分钟内增加了潜伏期。对于解热活性,与参比药物对乙酰氨基酚(250mg/kg)相比,在25、50和100mg/kg剂量下,[具体名称未给出]在30、60和120分钟时显著降低了发热。分子对接研究表明,与针对COX - 1和COX - 2同工酶的共结晶配体和参比药物(美洛昔康)相比,[具体名称未给出]呈现出更多的相互作用和更低的能量值。结果证明了[具体名称未给出]具有类似NSAIDs的镇痛和解热特性,表明其在疼痛治疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adea/7695913/dc439e20c61e/gr1.jpg

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