Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 31 2 2025 04 20 Cytotoxicity and Pro-apoptosis Activity of Synthetic Phenylacetamide Derivatives on Cancer Cells 179 186 10.34172/PS.025.40811 EN Omid Tavallaei https://orcid.org/0000-0001-5268-3016 Shayesteh Rezazadeh Marzieh Marzbany Alireza Aliabadi https://orcid.org/0000-0002-0514-2775 Journal Article 10.34172/PS.025.40811 2024 08 26 2025 01 12 Background: Despite advancements in cancer treatments, patient survival rates have not significantly improved due to drug resistance and side effects. Developing new anticancer drugs is crucial to providing more options and increasing chances of recovery, ultimately improving patient quality of life and global healthcare. We evaluated the cytotoxicity and pro-apoptosis activity of eleven phenylacetamide derivatives. Methods: The derivatives were first synthesized and characterized before being tested on MCF7, MDA-MB468, and PC12 cell lines using the MTT assay. We also assessed their potential anticancer effects through the TUNEL assay, caspase 3 activity testing, and real-time PCR. Results: Phenylacetamide derivatives, specifically 3d derivative, are highly effective against cancer cells by triggering apoptosis through upregulation of Bcl-2, Bax, FasL RNA expression, and caspase 3 activity. It has shown an IC50 value of 0.6±0.08 μM against MDA-MB-468 and PC-12 cells, while 3c and 3d also had significant cytotoxic effects against MCF-7 cells with IC50 values of 0.7±0.08 μM and 0.7±0.4 μM, respectively. Conclusion: Notably, phenylacetamide derivatives have shown great promise in controlling the growth and death of cancer cells. These derivatives have been found to possess the remarkable ability to stimulate both internal and external apoptotic pathways, which could greatly benefit conventional cancer treatment methods.