Nguyen Ha Thi, Vu Thien-Y, Vijay Kumar A, Hoang Vo Nguyen Huy, My Pham Thi Ngoc, Mandal Prashant S, Tatipamula Vinay Bharadwaj
Institute of Research and Development, Duy Tan University Da Nang 550000 Vietnam
Faculty of Medicine, Duy Tan University Da Nang 550000 Vietnam.
RSC Adv. 2021 Sep 2;11(47):29385-29393. doi: 10.1039/d1ra04407a. eCollection 2021 Sep 1.
Cyclooxygenase enzymes (COX1/2) have been widely studied and noted for their role in the biosynthesis of inflammation-induced proteins, prostaglandins and thromboxane. Multiple anti-inflammatory drugs have been developed to target these two enzymes, but most of them appeared to have notable adverse effects, especially on the cardiovascular system and lower gastrointestinal tract, suggesting an urgent need for new potent anti-inflammatory drugs. In this study, we screened twenty-two previously synthesized -aryl iminochromenes (NAIs) for their anti-inflammatory activity by performing COX-1/2 inhibitory assays. Five compounds (1, 10, 14, 15, and 20) that gave the best anti-inflammatory results were subjected to an anti-inflammatory assay using the formalin-induced hind rat paw oedema method, followed by studies using indomethacin and celecoxib as standard drugs. Among them, compound 10 stood out as the best candidate, and the percentage reduction in paw oedema at the dose of 20 mg kg body weight was found to be substantially higher with compound 10 than that with indomethacin. This is mostly due to the excellent suitability of the chromene-phenyl scaffold with a highly concentrated area of aromatic residues, which produced good π-π stacking interactions. Taken together, this study strongly suggests compound 10 as a potential candidate for anti-inflammatory drug research.
环氧化酶（COX1/2）已得到广泛研究，并因其在炎症诱导蛋白、前列腺素和血栓素生物合成中的作用而受到关注。已经开发出多种抗炎药物来靶向这两种酶，但其中大多数似乎都有显著的副作用，尤其是对心血管系统和下消化道，这表明迫切需要新的强效抗炎药物。在本研究中，我们通过进行COX-1/2抑制试验，筛选了22种先前合成的芳基亚氨基苯并二氢吡喃（NAIs）的抗炎活性。对五种抗炎效果最佳的化合物（1、10、14、15和20），采用福尔马林诱导大鼠后爪水肿法进行抗炎试验，随后以吲哚美辛和塞来昔布作为标准药物进行研究。其中，化合物10表现最为突出，发现在20 mg/kg体重剂量下，化合物10使爪水肿减轻的百分比显著高于吲哚美辛。这主要是由于苯并二氢吡喃-苯基支架具有极佳的适用性，其芳香族残基高度集中，产生了良好的π-π堆积相互作用。综上所述，本研究强烈表明化合物10是抗炎药物研究的潜在候选物。
