Asymmetric dimeric ent-kauranoids from Croton tonkinensis and their cytotoxicity

• Published in: Tetrahedron letters Vol. 60; no. 16; pp. 1099 - 1102
• Main Authors: Quan, Khong Trong, Tuan, Vu Van, Xuyen, Phi Thi, Tuan, Nguyen Quoc, Minh, Pham Thi Hong, Ito, Fumiaki, Thuong, Phuong Thien
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 18-04-2019
• Subjects: Asymmetric dimeric ent-kauranoids; Croton tonkinensis; ent-Kauranoids; HIF inhibition; Asymmetric dimeric ent-kauranoids; ent-Kauranoids; HIF inhibition; Croton tonkinensis
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2019.03.023

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•Two novel asymmetric dimeric ent-kauranoids were isolated from Croton tonkinensis.•A plausible biosynthetic pathway for two new dimers was proposed.•Major ent-kauranoid inhibited HIF-dependent transcription with an IC50 of 2.5 μM.•The first report on inhibition of an ent-kauranoid on HIF-dependent transcription.
Two asymmetric dimeric ent-kauranoids (1–2), together with three known ent-kauranoids (3–5), were isolated from the leaves of Croton tonkinensis. Their structures were determined on the basis of spectroscopic data. Diterpenoids with the 15-oxo-16-ene moiety showed significant inhibitory effects on the growth of eight human cancer cell lines. Additionally, the major diterpenoid 4 inhibited hypoxia-inducible factor-dependent transcription (HIF-1) in a luciferase reporter assay with an IC50 of 2.5 μM. The biosynthesis of the two new dimers was also proposed.