Herein, new N'-(substituted benzylidene)-3,5-dihydroxybenzohydrazide (1–13) series were synthesized, and their antioxidant, anticholinesterase, anti-tyrosinase, anti-urease, and antidiabetic activities were investigated together with in silico studies. The synthesized derivates were characterized using molecular spectroscopy, and the structure-activity relationships (SAR) were discussed for all tested biological assays. According to activity results, compound 3 exhibited excellent antioxidant activity in all tests, while compound 1 demonstrated the best acetylcholinesterase (AChE) inhibitory and butyrylcholinesterase (BChE) inhibitory activities. On the other hand, compound 11 showed excellent tyrosinase inhibitory (IC50:3.02±0.10 mM) and urease inhibitory (IC50:9.21±0.27 µM) activity. Moreover, among the synthesized compounds, compound 6 was detected as the best antidiabetic compound by inhibiting α-amylase (IC50:30.68±0.94 µM) and α-glycosidase (IC50:41.35±0.03 µM) enzymes, which were related with the antidiabetic activity. Molecular docking analysis confirmed AChE, BChE, tyrosinase, urease, α-amylase, and α-glucosidase inhibitory activities. In line with the findings obtained from in vitro bioactivity results and molecular docking analysis, hydrazone compounds are a suitable class of organic compounds for developing acetylcholinesterase, butyrylcholinesterase, urease, α-amylase, and α-glucosidase inhibitors.
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