4‐Furfuryloxymethyl‐1,2,3‐triazol‐1‐yl‐acetohydrazide Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors: Synthesis, Characterization and Comprehensive Biological Activity Studies

Abstract

AbstractThis study focused on the synthesis and evaluation of the biological activity of ten novel acetohydrazide hybrid derivatives, having furfuryloxy‐1,2,3‐triazole ring. All the target compounds were tested in vitro and in silico for their inhibitory potential against key enzymes: hAChE, hBChE, hCAI, and hCAII, all involved in significant physiological processes. Remarkably, two compounds, namely (E)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N′‐(4‐hydroxy‐3‐methoxybenzylidene)acetohydrazide (9) and (E)‐N′‐(4‐chlorobenzylidene)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)acetohydrazide (11), exhibited strong inhibitory activity. Compound 9 emerged as the top‐performing inhibitor for both hAChE (IC50 of 0.23 μM) and hBChE (IC50 of 0.74 μM). Additionally, compounds 9 and 11 displayed potent inhibitory effects on hCAI and hCAII, with IC50 values of 0.18 μM and 0.15 μM, respectively. Furthermore, in silico studies provided valuable insights into the interaction mechanisms and stability of the ligand‐protein complexes. Compound 9 demonstrated strong binding scores of −12.063 kcal/mol for hAChE and −9.359 kcal/mol for hBChE, while Compound 11 exhibited substantial scores of −7.040 kcal/mol for hCAI and −8.216 kcal/mol for hCAII. In conclusion, they stand out as promising inhibitors of hAChE, hBChE, hCAI and hCAII enzymes. Their inhibitory activity, supported by low IC50 values, indicated their potential to inhibit enzymes associated with neurological and metabolic processes.