Background/Objectives: This study evaluated the antifungal, enzyme inhibitory, and anticancer properties of the ethyl acetate (EtOAc) leaves extract of Rubus ulmifolius Schott using in vitro assays and in silico analysis. Methods: Antifungal activity was assessed against five fungal strains by measuring inhibition zones. Enzyme inhibition assays were conducted for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and urease. Antiproliferative effects were tested against HT-29 colorectal, SK-OV-3 ovarian, and A549 lung cancer cells using the MTT assay. Network pharmacology and molecular docking analyses were performed on major compounds previously identified by GC–MS (gallic acid, caffeic acid, catechin, and fructofuranose) to uncover the potential mechanisms of the plant in colorectal and ovarian cancers. Results: The extract displayed notable antifungal activity, particularly against Penicillium sp., Aspergillus fumigatus, and Candida albicans, with inhibition zones of 22.5 ± 0.7 to 26.8 ± 1.3 mm. Enzyme assays revealed moderate inhibition of AChE (IC₅₀ = 92.94 ± 1.97 µg/mL), weaker activity against BChE (IC₅₀ = 274.93 ± 2.32 µg/mL), and modest inhibition of urease (IC₅₀ = 262.60 ± 1.41 µg/mL). The extract exhibited strong antiproliferative effects against HT-29 and SK-OV-3 cells (IC₅₀ = 2.41 ± 0.13 and 4.63 ± 0.26 µg/mL, respectively), whereas activity against A549 lung cancer cells was limited. Network pharmacology predicted 52 and 44 overlapping target genes between the major compounds and colorectal and ovarian cancers, respectively. Protein–protein interaction networks identified hub genes for each cancer type, with key shared targets including EGFR, ESR1, PTGS2, and STAT3. Molecular docking confirmed favorable binding between these targets and the compounds, particularly catechin, which showed interactions comparable to those of reference inhibitors. Conclusions: These findings suggest that R. ulmifolius may possess multi-target antifungal, neuroprotective, and anticancer potential, warranting further in vitro pharmacological and preclinical validation.

Lung and ovarian cancers account for substantial cancer morbidity and mortality worldwide. Plant-derived natural products represent promising alternatives in cancer therapy because of their structural diversity and ability to target multiple signaling pathways. Prosopis species are ethnomedicinal plants traditionally known for their antimicrobial, anti-inflammatory, and antioxidant activities; however, their anticancer potential remains poorly explored. This study evaluates the anticancer properties of extracts of Prosopis cineraria, Prosopis farcta, and Prosopis juliflora, the Prosopis species growing in Qatar, against human lung (A549) and ovarian (SK-OV-3) cancer cells. Gas chromatography–mass spectrometry (GC–MS) was used to characterize their phytochemical composition. The cytotoxicity and anti-migratory activity of the three extracts were evaluated. Western blot analysis was performed to investigate the molecular effects of the extracts on proliferation- and apoptosis-related proteins. GC–MS profiling identified diverse low-molecular-weight bioactive compounds across the extracts, including several compounds detected only in P. juliflora, which exhibited the most potent cytotoxicity toward A549 and SK-OV-3 cells. All three extracts inhibited cancer cell migration, with P. juliflora showing the strongest effect. Furthermore, P. juliflora reduced the expression of proliferation and survival markers and increased the expression of pro-apoptotic proteins. These findings identify P. juliflora as the most active of the three tested Prosopis extracts and support further investigation of its in vitro anticancer potential.