Design, synthesis and antiproliferative activity of oxadiazole derivatives as potent glycogen synthase kinase-3/histone deacetylase 6 dual inhibitors
Abstract
A series of oxadiazole-based dual inhibitors targeting GSK3 and HDAC6 were rationally designed by integrating key pharmacophores into a single molecule. Among these derivatives, 4-(((5-(benzo[d][1, 3]dioxol-5-yl)-1,3,4-oxadiazol-2-yl)thio)methyl)-N-hydroxybenzamide (15i) was identified as the most potent compound with IC50 of 5.50, 69 nM and 88 nM against HDAC6, GSK3α and GSK3β, respectively. 15i also exhibited potent cytotoxicity against the AGS cancer cell line, with IC50 values in the submicromolar range. Molecular docking simulation confirmed that 15i fitted well into the active sites of both HDAC6 and GSK3β. These findings establish compound 15i as a promising candidate for further evaluation.
Fields of Study & Subjects
Histone Deacetylase Inhibitors Research
Cholinesterase and Neurodegenerative Diseases
Nuclear Receptors and Signaling
Publication details
- Journal / source
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Publisher
- Informa UK Limited
- Volume
- 41
- Issue
- 1
- Pages
- 2627711–2627711
- Publication date
- 23 February 2026
- Language
- EN