Elif Yardimci
| Novel N-Phenylacetamide Derivatives: In Vitro and In Silico Evaluation Against Prostate Cancer |
| Yardimci Elif 1,2, Erzurumlu Yalcin 3, and Yildiz Ilkay 4 1 Ankara University, Graduate School of Health Science, Ankara, Türkiye 2 Agri Ibrahim Cecen University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Agri, Türkiye 3 Süleyman Demirel University, Faculty of Pharmacy, Department of Biochemistry, Isparta, Türkiye 4 Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Türkiye |
| Abstract Prostate cancer is among the most prevalent malignancies in men worldwide and remains a significant challenge in cancer therapy. Although numerous therapeutic options and drugs are currently used, the development of drug-resistant cancer cells and limited clinical efficacy highlight the need for new alternative therapeutic strategies [1]. N-phenylacetamide is a scaffold associated with a wide range of biological activities, including anticancer, antifungal, antibacterial, antileishmanial, antidepressant, anticonvulsant, antimalarial, antiviral, analgesic, and antipyretic activities [2]. Moreover, numerous anticancer drugs containing an amide moiety in their structures are currently used in cancer therapy. In this study, a series of novel N-(2-hydroxy-4-chlorophenyl)acetamide derivatives were designed and synthesized [3] as potential anticancer agents and evaluated for the cytotoxicity against non-neoplastic (PNT1A) and neoplastic (LNCaP and DU145) human prostate cell lines using colorimetric-based WST-1 cell viability test [4], with etoposide serving as the reference drug. To investigate the molecular basis of these effects, in silico studies including molecular docking and ADME predictions were performed using Cresset Flare. The N-phenylacetamide derivatives were docked into the androgen receptor obtained from the Protein Data Bank (PDB:5V8Q) to assess binding interactions, while computational ADME analysis provided insights into their pharmacokinetic properties and drug-likeness. In vitro studies of the synthesized compounds demonstrated significant anticancer activity against prostate cancer. Furthermore, molecular docking studies revealed binding energies consistent with the in vitro results. In conclusion, these N-phenylacetamide derivatives may represent promising candidates for the treatment of prostate cancer. Acknowledgments: We thank the Research Fund of Ankara University Grant No: TDK-2025-4460 for financial support of this study. |
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