Gastroprotective activity of ent-beyerene derivatives in mice: Effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls

  • Bioorg Med Chem Lett. 2015 Jul 15;25(14):2813-7. doi: 10.1016/j.bmcl.2015.04.095.
Teresa Parra  1 ,  Julio Benites  2 ,  Lina M Ruiz  3 ,  Beatriz Sepulveda  4 ,  Mario Simirgiotis  5 ,  Carlos Areche  6
Affiliations
  • 1. Departamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
  • 2. Facultad de Ciencias de la Salud, Universidad Arturo Prat., Iquique, Chile.
  • 3. Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
  • 4. Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Quillota 980, Viña del Mar, Chile.
  • 5. Laboratorio de Productos Naturales, Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Antofagasta, Chile.
  • 6. Departamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. Electronic address: [email protected].
PMID: 26009162 DOI: 10.1016/j.bmcl.2015.04.095
Abstract

Seventeen compounds (2-18) synthetized from the diterpenoid ent-beyer-15-en-18-ol (1) isolated from aerial part of Baccharis tola were tested for their gastroprotective activity on the model of HCl/EtOH-induced gastric lesions in mice. Furthermore cytotoxicity test toward fibroblasts and AGS cells were performed. The results showed that compound 1 (ED50=50 mg/kg), 2, 6 and 13 were the most active regarding gastroprotective activity. Compounds 8-10 and 17-18 showed the lowest cytotoxicity toward fibroblasts and AGS cells. Regarding to mode of gastroprotective action, the effect elicited by 6 (50 mg/kg) was reversed by Indomethacin but not by N-ethylmaleimide, N(G)-nitro-L-arginine methyl ester or ruthenium red, which suggests that prostaglandins are involved in the mode of gastroprotective action of 6.

Keywords
Baccharis tola; Diterpenoids; Gastric ulcer; Semisynthetic derivatives; ent-Beyerene.