Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis

Eight new clerodane diterpenoids (1−8) were isolated from the twigs of Casearia graveolens. Their structures were determined by comprehensive analysis of NMR, HRESIMS, and ECD data. Besides structure elucidation, surface plasmon resonance (SPR) experiments were performed to investigate the molecular interactions, and compound 8 was found to have good affinity with VEGFR-2, a target regulating tumor angiogenesis to combat cancer. Subsequent in vivo anti-angiogenetic experiments disclosed that compound 8 inhibited angiogenesis and showed in vivo antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenografts. Compound 8 may be considered as a promising anticancer lead compound targeting VEGFR-2 to block tumor angiogenesis.