Drug repurposing study of selected antidepressants as anti-cancer agents by in silico

Drug repurposing offers a cost-effective and time-efficient strategy to identify new therapeutic applications for approved drugs, particularly in challenging diseases such as cancer. The present study aimed to evaluate the anticancer potential of selected antidepressants using in silico molecular docking against key cancer-associated targets. Selective serotonin reuptake inhibitors and related antidepressants, including fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, dapoxetine, and moclobemide, were screened against Histone Deacetylase (HDAC) and mammalian Target of Rapamycin (mTOR), two proteins critically involved in tumor growth and progression. Three-dimensional structures of ligands and proteins were retrieved from public databases and prepared for docking analysis. Molecular docking was performed using AutoDock Vina, and binding interactions were analyzed to determine affinity and stability in comparison with the standard anticancer drug temozolomide.
The results demonstrated that several antidepressants exhibited significant binding affinities toward both targets. Dapoxetine showed the strongest interaction with HDAC, while paroxetine demonstrated the highest affinity for mTOR, with docking scores comparable to or better than temozolomide. Key interactions included hydrogen bonding and hydrophobic contacts within the active sites of both proteins.
In conclusion, the findings suggest that selected antidepressants possess promising anticancer potential through stable interactions with HDAC and mTOR. These results support further experimental validation and highlight drug repurposing as a viable approach for developing alternative therapeutic strategies against cancer, particularly glioblastoma.