Year: 2022
Type: article
Abstract: In the current investigation, fifteen novel imidazole-pyridine-based molecules were synthesized and tested against cell lines of the lung (H1299) and colon (HCT116) adenocarcinomas by proliferation assay. The results demonstrated that compounds 5a, 5d, 5e, and 5f were the most active (IC50<30 µM). Based on recent literature and the current results, the glycogen synthase kinase-3β (GSK-3β) protein was investigated in-silico as a possible target. The molecular docking and QSAR revealed an excellent binding affinity of the selected imidazole-pyridine compounds to GSK-3β. Notably, GSK-3β protein levels were significantly upregulated in hepatocellular liver carcinoma (LIHCs) tissues and negatively affected patient prognosis. Consequently, the compounds were evaluated on liver cancer cell lines (HepG2, HUH-7, and PLC/PRF/5) by the MTT assay, and 5d showed the highest antitumor activity. This study offers new compounds with interesting biological activity on GSK-3β as a target, exhibiting a potential therapeutic impact for hepatocellular carcinoma patients.
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,300
OpenAlex ID: W4308326590