Akademik Veri Yönetim Sistemi
ACS OMEGA, cilt.10, sa.38, ss.43916-43931, 2025 (SCI-Expanded, Scopus)
Diabetes mellitus affects over 500 million people globally and is expected to rise significantly in the coming decades. Existing antidiabetic drugs, including alpha-glucosidase and alpha-amylase inhibitors, often exhibit side effects and limited efficacy, prompting the search for safer alternatives. Hydrazone derivatives have shown promising antidiabetic activity due to their structural diversity and enzyme-targeting potential. In this study, 10 novel hydrazone compounds were synthesized and evaluated for their inhibitory effects against alpha-amylase and alpha-glucosidase. Compounds 8 and 10 showed the highest dual inhibition: compound 8 with IC50 = 30.21 +/- 0.16 mu M (alpha-amylase) and 38.06 +/- 0.80 mu M (alpha-glucosidase); compound 10 with IC50 = 34.49 +/- 0.37 and 40.44 +/- 0.23 mu M, respectively. Cytotoxicity on HEK293 cells via MTT assay revealed IC50 values of 61.04 mu M (compound 7) and 69.25 mu M (compound 9), while other compounds and acarbose were nontoxic up to 100 mu M. In silico drug-likeness analysis showed that 80% of the compounds complied with Lipinski's rules, with topological polar surface area (TPSA) values ranging between 63 and 112 & Aring;2. Gastrointestinal absorption was high for 7 out of 10 compounds; none showed blood-brain barrier permeability. Molecular docking confirmed strong binding interactions of compounds 8 and 10 with both enzymes' active sites. These findings highlight hydrazone scaffolds as potent and safe candidates for further antidiabetic drug development.