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功能化杂环氟喹诺酮衍生物在四氯化碳诱导的大鼠肝损伤中的抗氧化活性和肝保护作用

Antioxidant activity and hepatoprotective effects of functionalized heterocyclic fluoroquinolone derivatives in carbon tetrachloride-induced liver injury in rats.

作者信息

Al-Hiari Yusuf, Al-Qirim Tareq, Suleiman Manal, Kasabri Violet, Alwahsh Mohammad, Abumansour Hamza

机构信息

School of Pharmacy, The University of Jordan, Queen Rania Street, Amman, 11942, Jordan.

School of Pharmacy, AL-Zaytoonah University of Jordan, Amman, Jordan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 7. doi: 10.1007/s00210-025-04341-2.

Abstract

Metalloenzymes have emerged as substantial therapeutic targets in the pathogenesis of various human health conditions. Fluoroquinolones' (FQs) derivatives of reduced nuclei harbor privileged scaffolds with versatile biological activities (antimicrobial, anti-inflammatory, selective antiproliferation and antilipolysis/antidiabesity). Highly functionalized lipophilic FQs (6e, 4a, and 6f) with prominent in vitro DPPH radical scavenging capacities were fed orally (20 mg/kg body weight) for 3 days to adult male Wistar rats (200 ± 10) g of i.p.-CCl4 inflicted hepatic oxidative injury. In comparison to the untreated control group of CCl4 alone, rats treated with FQ compounds had a reduction in ALT levels (by 78.3%, 79.6%, and 77.9%, respectively), a reduction in AST levels (by 73.0%, 70.5%, and 61.6% respectively), and SOD levels resumed normality (by 142.8%, 168.6%, and 160%, respectively). Albumin levels were restored to normality (by 21.7%, 34.8%, and 34.9%, respectively), as well as the total antioxidative status (TAS) that was normalised alike (by 448.6%, 457.1%, and 468.6%, respectively). As chelation can be the highly plausible molecular antioxidation mechanism, the C-8-C-7 ethylene diamine divalent and trivalent chelator groups, lipophilicity, acidity, and size are among the key structural features required for FQs antioxidant effectiveness. Furthermore, FQs' total H-B capabilities increase the total number of H-B donner/acceptors available for chelation.

摘要

金属酶已成为各种人类健康疾病发病机制中的重要治疗靶点。含氟喹诺酮类(FQs)的去核衍生物具有具有多种生物活性(抗菌、抗炎、选择性抗增殖和抗脂解/抗糖尿病)的特殊骨架。将具有显著体外DPPH自由基清除能力的高度官能化亲脂性FQs(6e、4a和6f)以20mg/kg体重口服给药成年雄性Wistar大鼠(200±10)g,这些大鼠因腹腔注射四氯化碳而遭受肝氧化损伤。与仅用四氯化碳处理的未治疗对照组相比,用FQ化合物处理的大鼠的谷丙转氨酶(ALT)水平降低(分别降低78.3%、79.6%和77.9%),谷草转氨酶(AST)水平降低(分别降低73.0%、70.5%和61.6%),超氧化物歧化酶(SOD)水平恢复正常(分别恢复142.8%、168.6%和160%)。白蛋白水平恢复正常(分别恢复21.7%、34.8%和34.9%),总抗氧化状态(TAS)也恢复正常(分别恢复448.6%、457.1%和468.6%)。由于螯合可能是高度合理的分子抗氧化机制,C-8-C-7乙二胺二价和三价螯合基团、亲脂性、酸度和大小是FQs抗氧化有效性所需的关键结构特征。此外,FQs的总氢键能力增加了可用于螯合的氢键供体/受体的总数。

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