Cyclic imides containing 3-benzenesulfonamide, oxime, and β-phenylalanine derivatives were synthesised and evaluated to elucidate their in vivo anti-inflammatory and ulcerogenic activity and in vitro cytotoxic effects. Most active anti-inflammatory agents were subjected to in vitro COX-1/2 inhibition assay. 3-Benzenesulfonamides (2-4, and 9), oximes (11-13), and β-phenylalanine derivative (18) 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 4, 9, 12, 13, and 18 possessed ED50 of 35.4-45.3 mg kg-1 relative to that of celecoxib (34.1 mg kg-1). For the cytotoxic evaluation, the selected derivatives 2-6 and 8 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 (2-5, and 9), acetophenone oxime (11-14, 18, and 19) exhibited high selectivity against COX-2 with SI > 55.6-333.3 relative to that for celecoxib [SI > 387.6]. β-Phenylalanine derivatives 21-24 and 28 were non-selective towards COX-1/2 isozymes as indicated by their SI of 0.46-0.68.

中文翻译：

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带有 3-苯磺酰胺、肟和 β-苯丙氨酸支架的环状酰亚胺的合成、抗炎、细胞毒性和 COX-1/2 抑制活性：分子对接研究。


合成并评估了含有 3-苯磺酰胺、肟和 β-苯丙氨酸衍生物的环状酰亚胺，以阐明其体内抗炎和溃疡形成活性以及体外细胞毒性作用。大多数活性抗炎剂均进行了体外 COX-1/2 抑制测定。 3-苯磺酰胺（2-4 和 9）、肟（11-13）和 β-苯丙氨酸衍生物（18）显示出潜在的抗炎活性，相对于塞来昔布和双氯芬酸（85.6 和 83.4%），水肿抑制率为 71.2-82.9% ， 分别）。大多数活性环状酰亚胺 4、9、12、13 和 18 相对于塞来昔布 (34.1 mg kg-1) 的 ED50 为 35.4-45.3 mg kg-1。对于细胞毒性评估，与标准药物伊马替尼 (PCE = 20/59) 相比，所选衍生物 2-6 和 8 在 10 μM 时表现出弱的阳性细胞毒性作用 (PCE = 2/59-5/59)。带有 3-苯磺酰胺（2-5 和 9）、苯乙酮肟（11-14、18 和 19）的环状酰亚胺对 COX-2 表现出高选择性，相对于塞来考昔，SI > 55.6-333.3 [SI > 387.6] 。 β-苯丙氨酸衍生物 21-24 和 28 对 COX-1/2 同工酶没有选择性，其 SI 为 0.46-0.68。