TY - JOUR
T1 - Gastroprotective effects of new diterpenoid derivatives from Azorella cuatrecasasii Mathias & Constance obtained using a β-cyclodextrin complex with microbial and chemical transformations
AU - Sepúlveda, Beatriz
AU - Quispe, Cristina
AU - Simirgiotis, Mario
AU - García-Beltrán, Olimpo
AU - Areche, Carlos
PY - 2016/1/1
Y1 - 2016/1/1
N2 - © 2016 Elsevier Ltd 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 20 mg/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.
AB - © 2016 Elsevier Ltd 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 20 mg/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.
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U2 - 10.1016/j.bmcl.2016.05.081
DO - 10.1016/j.bmcl.2016.05.081
M3 - Article
SP - 3220
EP - 3222
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
ER -