氧化应激和炎症在宏观/微观血管并发症中起着关键作用。酚类化合物及其衍生物显示出作为治疗癌症、代谢性疾病和心血管疾病的药物的潜力。凭借其抗氧化和抗炎作用，这些化合物具有减轻血管并发症和改善整体健康的潜力。本研究旨在通过体外、体内和计算机模拟的方法评估五种2-甲氧基酚衍生物(T2、T5、T6、T7和T8)作为抗氧化剂、抗炎剂和血管松弛剂的治疗潜力。其中，T2对2, 2-二苯基-1-苯基蚀蚀苦味素(DPPH)自由基、一氧化氮(NO)自由基、羟基(OH)自由基和铁螯合(IC50= 34.83 µg/mL)具有显著的抗氧化潜力(IC50= 34.36 µg/mL)。分子对接分析确认了所有衍生物，特别是T2，与目标蛋白ACE(-7.7 Kcal/mol)、ECE-1(-7.9 Kcal/mol)和COX-1(-7.8 Kcal/mol)之间具有良好的结合能。所有化合物在体外、体内和计算机模拟评估中显示出令人满意的物理化学和药物动力学特性，并且表现出最小或无毒性。在高钾(80mM)预收缩的Sprague Dawley大鼠的离体主动脉环中，T2以剂量依赖方式诱导血管舒张，并且与维拉帕米相比将钙响应曲线向右移。T2还显示出显著的剂量依赖性血小板聚集抑制作用，IC50为21.29 µM。除T7外的所有衍生物均表现出内源抗氧化剂即过氧化氢酶(CAT)、过氧化物酶(POD)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的显著保护，并显著抑制了血清中的炎症标志物即一氧化氮(NO)、过氧化物(TBARS)、白介素-6(IL-6)和环氧合酶-2(COX-2)。研究得出结论，T2具有显著的抗氧化潜力和血管舒张效应，并具备适当的药物动力学特性，使其成为进一步在心血管疾病中进行分子研究的有希望的引领化合物。© 2023年作者。由Elsevier Masson SAS发表。保留所有权利。

Oxidative stress and inflammation play crucial roles in macro/microvascular complications. Phenolic compounds and their derivatives show promise as therapeutic agents for diseases like cancer, metabolic disorders, and cardiovascular diseases. With their antioxidant and anti-inflammatory properties, these compounds hold potential for mitigating vascular complications and improving overall health.This study aimed to assess the therapeutic potential of five 2-methoxy phenol derivatives (T2, T5, T6, T7, and T8) as antioxidants, anti-inflammatory agents, and vasorelaxants using in vitro, in silico, and in vivo approaches.Among all, T2 exhibited substantial antioxidant potential against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals with IC50 (27.97 µg/mL), nitric oxide (NO) radicals (IC50 = 34.36 µg/mL), hydroxyl (OH) radicals (IC50 = 34.83 µg/mL) and Iron chelation (IC50 = 24.32 µg/mL). Molecular docking analysis confirms that all derivatives, particularly T2, exhibit favorable binding energies with the target proteins, ACE (-7.7 Kcal/mol), ECE-1 (-7.9 Kcal/mol), and COX-1 (-7.8 Kcal/mol). All of the compounds demonstrated satisfactory physicochemical and pharmacokinetic characteristics, and showed minimal to no toxicity during in silico, in vitro, and in vivo assessments. In isolated aortic rings from Sprague Dawley rats, pre-contracted with high K+ (80 mM), T2 induced vasorelaxation in dose dependent manner and shifted calcium response curves to the right as compared to verapamil. T2 also showed substantial platelet aggregation inhibition in a dose dependent manner with IC50 21.29 µM. All derivatives except T7 exhibited significant conservation of endogenous antioxidants i.e. catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and reduced glutathione (GSH) and significantly suppressed serum levels of inflammatory markers i.e. nitric oxide (NO), peroxides (TBARS), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2).The study concludes that T2 has significant antioxidant potential and vasorelaxant effects with adequate pharmacokinetics, making it a promising lead compound for further molecular investigation in cardiovascular disorders.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.