Pyrazole-thiazole hybrids: Synthesis, computational studies and impact on digestive enzymes

Abstract

In this study, the syntheses of some pyrazole-thiazole hybrids and their cyanoacrylate derivatives have been reported. 1H NMR, 13C NMR, LC-MS, and IR spectroscopy were used to characterize all the synthesized compounds. DFT studies have been employed to assess the electronic properties of the synthesized compounds. To ensure the necessary metabolization of the synthesized compounds, their safety profiles were assessed using the Vnn-ADMAT tool. Docking studies investigated the interactions between the synthesized compounds (6a-h and 8a-h) and the active sites of gastric enzymes α-Amylase, Trypsin, and Pepsin with binding affinities (kcal mol−1) ranging from 6.0 to 8.1, 6.7 to 8.5, and 7.7 to 8.6, respectively. Both pyrazole-thiazole hybrids and their cyanoacrylate derivatives demonstrated efficient anti-gastric activities. Varying levels of inhibition were observed among the analogs, such as compound 8f exhibiting the highest inhibitory activity at 61.93 % against α-Amylase at 10−7M, compound 6e showed best inhibition at 68.09 % against Trypsin at 10−7M, and compound 6c displayed remarkable inhibition at 69.51 % against Pepsin at 10−7M. The synthesized compounds exhibited selectivity for α-Amylase.