Design and synthesis of terephthalic dihydrazide analogues as dual inhibitors of glycation and urease

Abstract

The overexpression of urease is the root cause of peptic ulcers and gastritis. Therefore, introducing new inhibitors against urease is a possible therapeutic approach to overcoming the pathogenesis; for instance, limiting the risk of development of urinary calculi. Moreover, glycation is the leading cause of several complications. Thus, in this study, we synthesized novel terephthalic dihydrazide analogues and evaluated their biological importance. These terephthalic dihydrazide analogues were characterized using advanced spectroscopic techniques, such as ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS (ESI⁺), and FT-IR. Fortunately, 6 of the 11 synthesized compounds exhibited urease inhibitory capability, and 8 compounds exhibited anti-glycation capability. Compounds 13–14, 20 and 23 showed significant urease inhibition with IC₅₀ values of 63.12 ± 0.28, 65.71 ± 0.40, 49.2 ± 0.49 and 51.45 ± 0.39 μM, respectively. Meanwhile, they exhibited potent anti-glycation activity with IC₅₀ values of 67.53 ± 0.46, 68.06 ± 0.43, 48.32 ± 0.42 and 54.36 ± 0.40 μM, respectively. Molecular docking of active urease inhibitors showed their good binding at the entrance of the active site and good correlation with our in vitro results.