Bukhari Syed Nasir Abbas, Lauro Gianluigi, Jantan Ibrahim, Fei Chee Chin, Amjad Muhammad Wahab, Bifulco Giuseppe, Sher Hassan, Abdullah Iskandar, Rahman Noorsaadah Abd
Drug & Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
Dipartimento di Farmacia, Università di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
Future Med Chem. 2016 Oct;8(16):1953-1967. doi: 10.4155/fmc-2016-0062. Epub 2016 Sep 21.
In present study, the anti-inflammatory activities of a new series of benzimidazole derivatives were studied, investigating their inhibition of secretory phospholipase A, lipoxygenase, COXs and lipopolysaccharide-induced secretion of TNF-α and IL-6 in mouse RAW264.7 macrophages.
Synthesized compounds effectively inhibited proinflammatory enzymes and cytokines.
A strong inhibition of secretory phospholipases A2 was exhibited by benzimidazole derivatives with trifluoromethyl and methoxy substitutions at position 4 of attached phenyl, whereas compound 8 containing pyridine ring substituted with amino group showed very potent 5-lipoxygenase inhibition. Molecular docking experiments were carried out to elucidate the molecular basis of the observed inhibitory activities.
在本研究中，对一系列新型苯并咪唑衍生物的抗炎活性进行了研究，考察它们对分泌型磷脂酶A、脂氧合酶、环氧化酶以及脂多糖诱导的小鼠RAW264.7巨噬细胞中肿瘤坏死因子-α和白细胞介素-6分泌的抑制作用。
合成的化合物有效抑制了促炎酶和细胞因子。
在连接苯基的4位带有三氟甲基和甲氧基取代基的苯并咪唑衍生物对分泌型磷脂酶A2表现出强烈抑制作用，而含有氨基取代吡啶环的化合物8对5-脂氧合酶显示出非常强的抑制作用。进行了分子对接实验以阐明所观察到的抑制活性的分子基础。
