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.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents

“…1 H NMR spectra of products 9a−f showed in each case a singlet signal at δ = 7.40−7.48 ppm corresponding to H-5 of thiazole ring. 44 In IR, the bands of (C�O) group of compounds 11a and 11b were revealed at 1700 45 and 1695 46 cm −1 , respectively.…”

Synthesis, Characterization, and In Silico Studies of Novel Spirooxindole Derivatives as Ecto-5′-Nucleotidase Inhibitors

“…The comparison of some reported newly developed ecto-5′-NT inhibitors is shown in Table S4, and it has been observed that novel spiroindoline-pyrazolo [3,4-b]pyridine derivatives are more potent than benzenesulfonyl hydrazide based, 38 pyrazolopyridine based, 20 pyridinebenzanilide based, 39 pyrrolopyridine based, 40 acetylpyrazole based, 37 and naphthalene sulfonic acid based 14 scaffolds. When we mapped the structure of 1-methylspirooxindole-pyrazolo [3,4-b]pyridines with reported inhibitors, it showed the presence of two moieties, a 1-methylspirooxindole heterocycle and pyrazolo[3,4-b]pyridine ring, with amino and amide functionalities which increased hydrophilicity and had a strong impact on inhibitory activity.…”

Bis(N′-(3-chlorobenzoyl)isonicotinohydrazide)iron(III) Complex

“…Isoniazid, also known as isonicotinylhydrazide (INH), is an antibiotic used for the treatment of tuberculosis. It has attracted much attention due to its demonstrated biological activity as an antituberculosis [7][8][9][10][11][12][13][14] and anticancer [15][16][17] agent.…”