Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Department of Pharmacology & Toxicolgy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Bioorg Chem. 2018 Oct;80:70-80. doi: 10.1016/j.bioorg.2018.05.018. Epub 2018 May 21.
A group of novel isoindoline hybrids incorporating oxime, hydrazone, pyrazole, chalcone or aminosulfonyl pharmacophores (9-14) was designed and characterized by spectral data and elemental analyses results. All newly synthesized compounds were evaluated as COX-2 inhibitors, anti-inflammatory and analgesic agents. Six hybrid derivatives (10b, 10c, 11a, 11d, 13, 14) were moderate COX-2 inhibitors (IC = 0.11-0.18 µM) close to standard celecoxib (IC = 0.09 µM). The most active compounds showed outstanding in vivo anti-inflammatory activity (% edema inhibition = 41.7-50, 1 h; 40.7-67.4, 3 h; 20-46.7, 6 h) better than reference drug diclofenac (% edema inhibition = 29.2, 1 h; 22.2, 3 h; 20, 6 h). Most compounds showed significant peripheral and/or central analgesic activity. The moderate selective COX-2 inhibitor; dimethoxychalcone 11d (SI = 103) displayed excellent anti-inflammatory activity (% edema inhibition = 45.8-59.3) and increased thermal pain threshold (50-92.85%) comparable to piroxicam (75%). Molecular docking studies have been established.
一组新型异吲哚类化合物，包含肟、腙、吡唑、查耳酮或氨基磺酰基药效团（9-14），通过光谱数据和元素分析结果进行了设计和表征。所有新合成的化合物均作为 COX-2 抑制剂、抗炎和镇痛药进行了评估。六个杂合衍生物（10b、10c、11a、11d、13、14）是中度 COX-2 抑制剂（IC=0.11-0.18µM），接近标准塞来昔布（IC=0.09µM）。最活跃的化合物表现出出色的体内抗炎活性（%水肿抑制=41.7-50，1h；40.7-67.4，3h；20-46.7，6h），优于参考药物双氯芬酸（%水肿抑制=29.2，1h；22.2，3h；20，6h）。大多数化合物表现出显著的外周和/或中枢镇痛活性。中度选择性 COX-2 抑制剂二甲氧基查耳酮 11d（SI=103）表现出出色的抗炎活性（%水肿抑制=45.8-59.3），并增加了热痛阈值（50-92.85%），与吡罗昔康相当（75%）。已经建立了分子对接研究。
