Design, Synthesis, and Evaluation of Cytotoxic Effects of Functional Fatty Acid Derivatives as Potential Antineoplastic Agents for Breast Cancer.

Background: Breast cancer is among the most prevalent cancers in women and is the leading cause of mortality among women worldwide. Although a definitive cure for breast cancer remains elusive, essential fatty acids offer a promising therapeutic avenue. Objectives: The present study aimed to synthesize 16 derivatives of docosahexaenoic acid (DHA) and linoleic acid (LA) and evaluate their anti-cancer properties in vitro. Methods: Fourteen derivatives of LA and DHA were synthesized using a coupling method, while two ethylenediamine derivatives were synthesized via an ester intermediate. Molecular modeling was conducted using AutoDock Vina software. The cytotoxic effects of all compounds were assessed using the MTT assay on breast adenocarcinoma (MCF-7) cells. The mechanism of cell death induction by derivatives with the most favorable EC Results: Docking results revealed that these compounds effectively interact with residues in the PTPB1 active site. All synthesized DHA and LA derivatives demonstrated cytotoxic effects on the MCF-7 cell line, with no significant cytotoxicity observed in normal human dermal fibroblasts (HDFs). Compounds D3 and L3, with EC Conclusions: The findings indicate that these functional fatty acid derivatives significantly reduce cancer cell viability. In addition to necrosis, compounds L3 and D3 induced apoptosis, with apoptosis rates of 20.5% and 47.1%, respectively.