Gastroprotective activity of synthetic coumarins: Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors

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• 作者：Beatriz Sepulveda^a ; Cristina Quispe^b ; Mario Simirgiotis^c ; Alfredo Torres-Bení ; tez^d ; Johanna Reyes-Ortí ; z^d ; Carlos Areche^e ; ^{areche@uchile.cl" class="auth_mail" title="E-mail the corresponding author} ; Olimpo Garcí ; a-Beltrá ; n^d ; ^{jose.garcia@unibague.edu.co" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Coumarins ; Gastroprotective ; Ulcer ; Heterocycles
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：26
• 期：23
• 页码：5732-5735
• 全文大小：423 K

文摘

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 g class="boldFont">6g> and g class="boldFont">10g> 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 g class="boldFont">6g> and g class="boldFont">10g> were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin g class="boldFont">6g>, 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 g class="boldFont">10g> the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.