Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):610-621. doi: 10.1080/14756366.2020.1722120.
Cyclic imides containing 3-benzenesulfonamide, oxime, and β-phenylalanine derivatives were synthesised and evaluated to elucidate their anti-inflammatory and ulcerogenic activity and cytotoxic effects. Most active anti-inflammatory agents were subjected to COX-1/2 inhibition assay. 3-Benzenesulfonamides (, and ), oximes (), and β-phenylalanine derivative () showed potential anti-inflammatory activities with 71.2-82.9% oedema inhibition relative to celecoxib and diclofenac (85.6 and 83.4%, respectively). Most active cyclic imides , , , , and possessed ED of 35.4-45.3 mg kg relative to that of celecoxib (34.1 mg kg). For the cytotoxic evaluation, the selected derivatives and exhibited weak positive cytotoxic effects (PCE = 2/59-5/59) at 10 μM compared to the standard drug, imatinib (PCE = 20/59). Cyclic imides bearing 3-benzenesulfonamide (, and ), acetophenone oxime (, , and ) exhibited high selectivity against COX-2 with SI > 55.6-333.3 relative to that for celecoxib [SI > 387.6]. β-Phenylalanine derivatives and were non-selective towards COX-1/2 isozymes as indicated by their SI of 0.46-0.68.
合成了含有 3-苯磺酰胺、肟和 β-苯丙氨酸衍生物的环状酰亚胺，并对其抗炎和致溃疡活性及细胞毒性进行了评价。将最具活性的抗炎剂进行 COX-1/2 抑制测定。3-苯磺酰胺（、和）、肟（）和 β-苯丙氨酸衍生物（）表现出潜在的抗炎活性，与塞来昔布和双氯芬酸（分别为 85.6%和 83.4%）相比，水肿抑制率为 71.2%-82.9%。最具活性的环状酰亚胺、、、、和 对 COX-1/2 的 ED 为 35.4-45.3 mg/kg，与塞来昔布（34.1 mg/kg）相当。对于细胞毒性评价，选择的衍生物和表现出较弱的阳性细胞毒性效应（PCE = 2/59-5/59），在 10 μM 时与标准药物伊马替尼（PCE = 20/59）相比。含有 3-苯磺酰胺（、和）、苯乙酮肟（、、和）的环状酰亚胺对 COX-2 具有高选择性，SI > 55.6-333.3，与塞来昔布相比[SI > 387.6]。β-苯丙氨酸衍生物和对 COX-1/2 同工酶没有选择性，其 SI 为 0.46-0.68。
