# Design, synthesis and antiproliferative activity of oxadiazole derivatives as potent glycogen synthase kinase-3/histone deacetylase 6 dual inhibitors

## TL;DR

Scientists designed a compound that inhibits two enzymes linked to cancer, showing strong activity in tests.

## Contribution

A new oxadiazole compound (15i) was developed as a dual inhibitor of GSK3 and HDAC6 with high potency.

## Key findings

- Compound 15i has IC50 values of 5.50 nM for HDAC6 and 69 nM and 88 nM for GSK3α and GSK3β, respectively.
- 15i showed potent cytotoxicity against AGS cancer cells with submicromolar IC50 values.
- Molecular docking simulations confirmed that 15i fits well into the active sites of HDAC6 and GSK3β.

## 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.