Syntheses and structure-activity relationship study of santamarine, douglanine, dihydrosantamarine and four series of 1-/3-oxygenated eudesman-12, 6α-olides. (27th August 2022)

• Record Type: Journal Article
• Authors: Wang, Rui; Toyama, Daisuke; Arao, Kei; Shinozaki, Miwako; Ando, Mariko; Bai, Yuhua; Ando, Masayoshi
• Is Part Of: Tetrahedron. Volume 121(2022)
• Publication Date: 2022-08-27
• Subjects: 1-/3-Oxygenated eudesman-12, 6α-lactones -- Anti-inflammation -- Cytotoxicity -- Douglanine -- Santamarine -- Syntheses; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2022.132912
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Herein, we report the syntheses and structure-activity relationships of Santamarine, Douglanine, dihydrosantamarine, 1-oxygenated and 3-oxygenated eudesman-12, 6 α -lactones. The anti-inflammatory and anti-cancer activities were measured by the inhibition on induction of intercellular adhesion molecule (ICAM-1), killing function of cytotoxic T lymphocytes (CTLs), and cytotoxic activities to cell lines (VA-13, HepG-2, and WI-38), respectively. α -Methylene- γ -lactones 13 with a 1-oxo-2-en moiety showed significant inhibition toward ICAM-1(IC50 12.8 μM), the killing function of CTLs (IC50 11.0 μM) and the VA-13 cell line (IC50 2.84 μM), 21 with α -bromo-ketone moiety showed significant inhibition to VA-13(IC50 1.85 μM). Both 13 ((cell viability)/(inhibitory activity of ICAM-1) = 6.0-fold, WI-38/VA-13 = 1.28-fold) and 21 (WI-38/VA-13 = 1.28-fold) were within safety satisfaction. To conclude, the α, β -unsaturated-ketone and α-bromo-ketone moieties were essential for α -methylene-eudesman-12, 6 α -olides' anti-inflammatory and anti-cancer activities. Graphical abstract: Image 1 Highlights: The synthesis and SAR study of eudesman-12, 6 α -lactones. The anti-inflammatory activities based on the induction of ICAM-1 and the killing function of CTLs; The anti-cancer activity based on the cytotoxic activities against cell lines VA-13, HepG2, and WI-38. α -Methylene- γ -lactones with α, β -unsaturated-ketones and with α -bromo-ketone moietes were the most anti-inflammatory and anti-tumor active eudesman-12, 6 α -lactones.