Gastroprotective effects of new diterpenoid derivatives from Azorella cuatrecasasii Mathias & Constance obtained using a β-cyclodextrin complex with microbial and chemical transformations.
Mulinane diterpenoids isolated from Azorella species have displayed gastroprotective effects in animal models. In this study we have transformed the main constituent, mulin-11,13-dien-20 oic acid from this plant using the filamentous fungus Mucor plumbeus and a β-cyclodextrin inclusion complex and we have obtained two main products with good yields (33% and 15% for compound 4 and 5, respectively) for further preparation of semisynthetic derivatives to evaluate their gastroprotective effects. In addition, one of the compounds isolated from Azorella cuatrecasasii was new (9-epi-13α-hydroxymulinene 1). Six new derivatives 4a-4c and 5a-5c were then prepared by simple chemical transformations. The structures of all compounds were elucidated by spectroscopic means based on 1D and 2D-NMR techniques. Some 8 diterpenes were evaluated for their gastroprotective effects in the ethanol/HCl-induced ulcer model in mice at 20mg/kg. The highest gastroprotective activity was shown by 7α,16-dihydroxymulin-11,13-dien-20-oic acid 5, which was higher than the reference drug lansoprazole, while 16-hydroxymulin-11,13-dien-20-oic acid 4 was as active as lansoprazole.
Departmento de Química, Universidad Andrés Bello, Viña del Mar, Chile.
Beatriz
B
Sepúlveda
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Cristina
C
Quispe
Laboratorio de Productos Naturales, Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Antofagasta, Chile.
Mario
M
Simirgiotis
Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 Calle 67, Ibagué 730001, Colombia. Electronic address: jose.garcia@unibague.edu.co.
Olimpo
O
García-Beltrán
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. Electronic address: areche@uchile.cl.
Carlos
C
Areche
D000438:Alcohols; D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006851:Hydrochloric Acid; D051379:Mice; D008968:Molecular Conformation; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
D000438:Alcohols; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D047392:beta-Cyclodextrins; D006851:Hydrochloric Acid
Azorella cuatrecasasii; Biotransformation; Gastric ulcer; Microbial transformation; Mulinane