In Vitro biological evaluation of some hybrid molecules bearing 2-quinoline as anti-inflammatory and anti-cancer agents

The wide range of therapeutic biological applications of thiosemicarbazone, 2-thiohydantoin, and thiazole derivatives has drawn the attention of scientists. Herein, a number of hybrid compounds having a 7-substituted-2(1H)-quinolin-3-yethylidene were created and verified using elemental analysis and several spectroscopic methods. 7-OH-3-CH3O-1H-quinolin-2-one (2) was obtained via the ammonlysis of 7-hydroxy-3-acetyl coumarin (1) with NH3 in the presence of anhydrous K2CO3 in EtOH. The condensation of (2) with thiosemicarbazide in ethanol in the presence of an acid catalyst afforded the thiosemicarbazone derivative (3). The cyclization of (3) with ClCH2COOEt and 4-chlorophenacyl bromide afforded the corresponding 2-thiohydantoin and thiazole derivatives (5 and 6). Acetyl derivatives (4, 7, and 8) were obtained via the acetylation of components (3, 5, and 6) with Ac2O. The results of the cytotoxic and anti-cancer activities of the synthesized component (5, 6, and 8) showed significant anti-proliferative potency against Kasumi-1 cells with IC50 values of 73.92, 79.90, and 93.43 mu M, respectively. The compound (6) was the most potent derivative that inhibits TNF-alpha at a fold change value of 0.25 fold, which is nearly the same as celecoxib 0.24 fold. The docking results revealed distinct interactions between compounds (5 and 6) with the TNF-alpha receptor binding pocket. As a result, the preliminary data approved that substituted quinolines displayed a significant pharmacological feature.