Al-Hiari Yusuf, Al-Qirim Tareq, Suleiman Manal, Kasabri Violet, Alwahsh Mohammad, Abumansour Hamza
School of Pharmacy, The University of Jordan, Queen Rania Street, Amman, 11942, Jordan.
School of Pharmacy, AL-Zaytoonah University of Jordan, Amman, Jordan.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 7. doi: 10.1007/s00210-025-04341-2.
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.
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。