alpha-Mangostin

α-Mangostin is a xanthone that has been found in G. mangostana and has diverse biological activities.^1,2,3,4,5 It inhibits fatty acid synthase and HIV-1 protease (IC₅₀s = 5.54 and 5.12 μM, respectively).^2,3 α-Mangostin is active against methicillin-sensitive and -resistant S. aureus strains (MICs = 1.57-12.5 μg/ml).¹ It inhibits nitric oxide and prostaglandin E₂ production in LPS-stimulated RAW 264.7 cells (IC₅₀s = 12.4 and 11.08 μM, respectively).⁴ α-Mangostin is an agonist of stimulator of interferon genes (STING) that binds to the C-terminal domain of STING (H232 variant) with a K_d value of 137 μM and induces expression of an IFN-β-luciferase reporter in HEK293T cells transfected with human STING (H232 variant) to a greater extent than cells expressing murine STING or human STING (R232 variant) when used at a concentration of 25 μM.⁶ α-Mangostin (20 mg/kg) prevents carrageenan-induced paw edema in mice. It decreases the viability of LNCaP, 22Rv1, DU145, and PC3 prostate cancer cells in vitro (IC₅₀s = 5.9, 6.9, 22.5, and 12.7 μM, respectively) and reduces tumor growth in a 22Rv1 mouse xenograft model when administered at a dose of 100 mg/kg.⁵

1.Iinuma, M., Tosa, H., Tanaka, T., et al.Antibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureusJ. Pharm. Pharmacol.48(8)861-865(1996) 2.Jiang, H.Z., Quan, X.F., Tian, W.X., et al.Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostanaBioorg. Med. Chem. Lett.20(20)6045-6047(2010) 3.Chen, S.-X., Wan, M., and Loh, B.-N.Active constituents against HIV-1 protease from Garcinia mangostanaPlanta Med.62(4)381-382(1996) 4.Chen, L.-G., Yang, L.-L., and Wang, C.-C.Anti-inflammatory activity of mangostins from Garcinia mangostanaFood Chem. Toxicol.46(2)688-693(2008) 5.Johnson, J.J., Petiwala, S.M., Syed, D.N., et al.α-Mangostin, a santhone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growthCarcinogenesis33(2)413-419(2012) 6.Zhang, Y., Sun, Z., Pei, J., et al.Identification of α-mangostin as an agonist of human STINGChemMedChem13(19)2057-2064(2018)