Synthesis of novel (E)-1-(2-(2-(4(dimethylamino) benzylidene) hydrazinyl)-4-methylthiazol-5-yl)ethanone derivatives as ecto-5′-nucleotidase inhibitors

Abstract

Ecto-5′-nucleotidase (e5′NT), a membrane-bound enzyme and an essential member of ecto-nucleotidases which regulates extracellular purinergic signalling. Their upregulation results in various disease conditions, for example, inflammation, hypoxia and cancer. Therefore, efforts have been made to synthesize potent and selective inhibitors of e5′NT. Here we have synthesized, characterized and evaluated six thiazole derivatives (3a–3f) as potent e5′NT inhibitors. Among all derivatives, the compound (E)-1-(4-methyl-2-(2-(pyridin-3-ylmethylene)hydrazinyl) thiazol-5-yl)ethanone (3a) exhibited maximum inhibition towards both human and rat enzymes. However, their potency against h-e5′NT was 24-fold higher than r-e5′NT. Only two compounds exhibited inhibitory behaviour towards r-e5′NT. The molecular structures of these derivatives were confirmed with the help of solid-state characterization through NMR (1H and 13C), FTIR and elemental analysis. Additionally, molecular docking was also implemented to explain putative bonding interaction between the active site of an enzyme and potent inhibitors.

Keywords

• ecto-5′-nucleotidase
• thiazole
• schiff base
• azomethines