TY - JOUR
T1 - Gastroprotective activity of synthetic coumarins
T2 - Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors
AU - Sepulveda, Beatriz
AU - Quispe, Cristina
AU - Simirgiotis, Mario
AU - Torres-Benítez, Alfredo
AU - Reyes-Ortíz, Johanna
AU - Areche, Carlos
AU - García-Beltrán, Olimpo
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20 mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole at 20 mg/kg and reducing gastric lesions by 75 and 76%, respectively. Then, in a second experiment, compounds 6 and 10 were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin 6, the protective effect was reduced by pre-treatment of the mice with N-ethylmaleimide and l-NAME suggesting that sulfhydryl compounds and endogenous nitric oxide are involved in its gastroprotective activity. While for coumarin 10 the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.
AB - Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20 mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole at 20 mg/kg and reducing gastric lesions by 75 and 76%, respectively. Then, in a second experiment, compounds 6 and 10 were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin 6, the protective effect was reduced by pre-treatment of the mice with N-ethylmaleimide and l-NAME suggesting that sulfhydryl compounds and endogenous nitric oxide are involved in its gastroprotective activity. While for coumarin 10 the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.
KW - Coumarins
KW - Gastroprotective
KW - Heterocycles
KW - Ulcer
UR - http://www.scopus.com/inward/record.url?scp=84995904527&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2016.10.056
DO - 10.1016/j.bmcl.2016.10.056
M3 - Artículo
C2 - 27810240
AN - SCOPUS:84995904527
VL - 26
SP - 5732
EP - 5735
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 23
ER -