Lipophilic Extracts of Portulaca oleracea L.: Analysis of Bioactive Fatty Acids Targeting Microbial and Cancer Pathways

<b>Background/Objectives:</b><i>Portulaca oleracea</i> L. (purslane) is a widely distributed plant known for its medicinal and nutritional properties. This study aims to evaluate the fatty acid composition and bioactivities of crude lipophilic extracts (chloroform/methanol 2:1) from purslane collected in Serbia and Greece, with a focus on its antimicrobial and anticancer potential. <b>Methods:</b> Chemical analysis was conducted to determine the fatty acid composition of the extracts. Antibacterial activity was assessed using standard microdilution assays, while antibiofilm assays evaluated the extracts' ability to inhibit biofilm formation. Cytotoxicity was tested on cancer cell lines (MCF7, HeLa, CaCo2, HepG2) and normal keratinocyte cells (HaCaT). Molecular docking and dynamics simulations were performed to explore the interactions of bioactive fatty acids with microbial and cancer-related proteins. <b>Results:</b> The analysis revealed significant levels of polyunsaturated fatty acids, with linoleic acid as the predominant fatty acid in both samples (31.42% and 34.51%). The Greek extract exhibited stronger antibacterial activity than the Serbian extract, particularly against <i>Aspergillus versicolor</i>, <i>Pseudomonas aeruginosa</i>, and <i>Staphylococcus aureus</i>. Antibiofilm assays showed up to 89.54% destruction at MIC levels, with notable reductions in exopolysaccharide and extracellular DNA production, especially for Greek samples. Cytotoxicity testing indicated moderate effects on cancer cell lines (IC₅₀ = 178.17-397.31 µg/mL) while being non-toxic to keratinocytes. Molecular docking identified strong interactions between key fatty acids and microbial and cancer-related proteins. <b>Conclusions:</b> These results highlight purslane's potential as a source of bioactive compounds, particularly in antimicrobial and anticancer applications. The findings suggest that purslane extracts could be developed for therapeutic purposes targeting microbial infections and cancer.