Disulfide-rich polysulfur alkaloids target vascular endothelial growth factor A through electronic duality and shape-responsive recognition.

ABSTRACT: Vascular endothelial growth factor A (VEGFA) is a pivotal driver of tumor-induced angiogenesis, yet its flat and featureless interface has long resisted small-molecule intervention. Here, we report the first systematic exploration of disulfide-rich polysulfur alkaloids, lissoclibadins (LCs), as a promising candidate for VEGFA inhibitors. Comprehensive structural, electronic, and molecular dynamics analyses reveal that the sulfur-enriched cores of LCs confer conformational plasticity and electronic duality, enabling shape-responsive recognition of VEGFA loop regions. Quantum chemical descriptors highlight pronounced ambiphilicity at sulfur centers, with LC1, LC4, LC7, and LC8 displaying elongated S-S bonds, low bond strength indices, and high softness, correlating with enhanced reactivity a

SUBMITTER: Mohanty B 

PROVIDER: S-EPMC12749042 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature