1,3,4-Oxadiazole derivatives as potential anti-glioma agents: synthesis, characterization, in vitro cytotoxic activity against HS683 cells, and molecular docking
TL;DR
The results position B2 as a lead compound for further development as an anti-glioma agent and Molecular docking against PI3Kα, CDK2, and FAK suggested possible binding modes for the active compounds.
Abstract
The 1,3,4-oxadiazoles were synthesized by acid-catalyzed condensation of the hydrazides with aromatic aldehydes to give the hydrazones, which were then oxidized to the corresponding 1,3,4-oxadiazoles using I 2 /K 2 CO 3 in DMSO. Characterization was carried out by FT-IR, 1 H NMR, 13 C NMR, and EI mass spectrometry. Human oligodendroglioma (HS683) cells and normal human astrocytes (NHA) were used to determine cytotoxicity and the selectivity index (SI). The MTT assay against HS683, using cisplatin as the reference drug, yielded IC 50 values lower than the IC 50 of cisplatin for all compounds. B2 was the most active compound, with the lowest IC 50 (37.71 µg/mL) and the highest SI (14.55). Molecular docking against PI3Kα, CDK2, and FAK suggested possible binding modes for the active compounds. All compounds satisfied Lipinski’s rule of five, were predicted to have high gastrointestinal absorption, and had no predicted P-glycoprotein substrate activity. These results position B2 as a lead compound for further development as an anti-glioma agent.