A copper(II)-based complex from mangrove endophytic fungus Fusarium proliferatum inhibits ovarian cancer in vitro via VEGF/VEGFR2 pathways and apoptosis factors

From a mangrove endophytic fungus, Fusarium proliferatum, four compounds were isolated. These compounds include a copper(II)-based complex (1), its ligand fusaric acid (2), and two fusaric acid derivatives (3, 4). Among them, compounds 1 and 4 are undescribed natural compounds. The elucidation of their structures, including absolute configurations, was accomplished through a combination of analytical techniques, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and single-crystal X-ray analysis. Compound 1 has exhibited inhibitory effects on the growth of ovarian cancer SKOV3 in vitro, primarily through its induction of mitochondrial membrane potential collapse in SKOV3 cells. Additionally, it has demonstrated the ability to activate key signaling molecules within the vascular endothelial growth factor (VEGF) pathway, particularly focal adhesion kinase (FAK) and its phosphorylated form (p-FAK), as well as protein kinase B (AKT) and its phosphorylated form (p-AKT), and extracellular signal-regulated kinases 1/2 (ERK1/2) and their phosphorylated forms (p-ERK1/2). As a result of these findings, compound 1 is now considered a promising copper-based candidate for both anticancer and antiangiogenic therapeutic applications.