It is well established that cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) play a vital role in the initiation and progression of inflammatory reactions. Hence, thiazole and thiazolidene-based pharmacophore molecules were synthesized to obtain dual COX-2 and 5-LOX inhibitory activity. The synthesis of target compounds has been achieved by a novel green strategy. In vitro COX-1, COX-2, and 5-LOX evaluation of these molecules have shown the potential for an improved anti-inflammatory profile. Most promising compound among the series (2-(diphenylamino)-4-(4-nitrophenyl)thiazol-5-yl)(naphthalen-1-yl)methanone 7h (IC₅₀ = 0.07 ± 0.02 μM) showed equivalent COX-2 inhibitory potency as that of positive control etoricoxib (IC₅₀ = 0.07 ± 0.01 μM) and an enhanced selectivity index of 115.14. Compound 7h exhibited 5-LOX IC₅₀ of 0.29 ± 0.09 μM and reference drug zileuton showed IC₅₀ of 0.15 ± 0.05 μM. In vivo studies of 7h including carrageenan-induced paw edema assay (63% inhibition of paw edema), antiulcer studies, biochemical assays, qRT-PCR analysis, and anticancer studies indicated that the present study has identified a good lead compound for the development of a potential anti-inflammatory drug having improved gastric safety profile.

众所周知，环氧合酶2（COX-2）和5-脂氧合酶（5-LOX）在炎症反应的发生和发展中起着至关重要的作用。因此，合成了噻唑和噻唑烷基药效团分子，以获得双重COX-2和5-LOX抑制活性。目标化合物的合成已通过新型绿色策略实现。这些分子的体外COX-1，COX-2和5-LOX评估显示出改善抗炎性的潜力。该系列（2-（二苯氨基）-4-（4-硝基苯基）噻唑-5-基）（萘-1-基）甲酮7h（IC ₅₀  = 0.07±0.02μM）中最有希望的化合物显示出等效的COX-2抑制作用阳性对照依托昔布的效价（IC ₅₀ = 0.07±0.01μM）和选择性指数115.14。化合物7h的5-LOX IC ₅₀为0.29±0.09μM，参比药物齐留通的IC ₅₀为0.15±0.05μM。7小时体内研究包括角叉菜胶诱导的爪水肿测定（抑制爪水肿63％），抗溃疡研究，生化测定，qRT-PCR分析和抗癌研究表明，本研究已经确定了一种良好的先导化合物，可用于治疗糖尿病。一种潜在的抗炎药，具有改善的胃安全性。