2016 |
Sepulveda, B; Quispe, C; Simirgiotis, M; Torres-Benitez, A; Reyes-Ortiz, J; Areche, C; Garcia-Beltran, O Gastroprotective Activity of Synthetic Coumarins: Role of Endogenous Prostaglandins, Nitric Oxide, Non-Protein Sulfhydryls and Vanilloid Receptors Artículo de revista Bioorganic & Medicinal Chemistry Letters, 26 (23), pp. 5732-5735, 2016, ISSN: 0960-894x. Resumen | Enlaces | BibTeX | Etiquetas: anhydrase applications, carbonic-anhydrases, coumarins, cysteine, defense derivatives, gastroprotective, glutathione, heck heterocycles, i, inhibition, isozymes reaction, scaffold, therapeutic ulcer @article{RN285, title = {Gastroprotective Activity of Synthetic Coumarins: Role of Endogenous Prostaglandins, Nitric Oxide, Non-Protein Sulfhydryls and Vanilloid Receptors}, author = { B. Sepulveda and C. Quispe and M. Simirgiotis and A. Torres-Benitez and J. Reyes-Ortiz and C. Areche and O. Garcia-Beltran}, url = {/brokenurl#<Go to ISI>://WOS:000389519100023}, doi = {10.1016/j.bmcl.2016.10.056}, issn = {0960-894x}, year = {2016}, date = {2016-01-01}, journal = {Bioorganic & Medicinal Chemistry Letters}, volume = {26}, number = {23}, pages = {5732-5735}, publisher = {2016 Elsevier Ltd.}, abstract = {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.}, keywords = {anhydrase applications, carbonic-anhydrases, coumarins, cysteine, defense derivatives, gastroprotective, glutathione, heck heterocycles, i, inhibition, isozymes reaction, scaffold, therapeutic ulcer}, pubstate = {published}, tppubtype = {article} } 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. |
2014 |
Aliaga, M E; Tiznado, W; Cassels, B K; Nunez, M; Millan, D; Perez, E G; Garcia-Beltran, O; Pavez, P Substituent Effects on Reactivity of 3-Cinnamoylcoumarins with Thiols of Biological Interest Artículo de revista Rsc Advances, 4 (2), pp. 697-704, 2014, ISSN: 2046-2069. Resumen | Enlaces | BibTeX | Etiquetas: alpha, beta-unsaturated chemical-reactivity, cysteine, density-functional-approach, disease, electrophilicity fluorescent, glutathione, ketones, michael probe, turn-on @article{RN195, title = {Substituent Effects on Reactivity of 3-Cinnamoylcoumarins with Thiols of Biological Interest}, author = { M.E. Aliaga and W. Tiznado and B.K. Cassels and M. Nunez and D. Millan and E.G. Perez and O. Garcia-Beltran and P. Pavez}, url = {/brokenurl#<Go to ISI>://WOS:000327849700027}, doi = {10.1039/c3ra44695f}, issn = {2046-2069}, year = {2014}, date = {2014-01-01}, journal = {Rsc Advances}, volume = {4}, number = {2}, pages = {697-704}, abstract = {The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, gamma-glutamylcysteine and glutathione with 3-cinnamoylcoumarin derivatives (ChC1-ChC4) in aqueous solution (30 degrees C, ionic strength 0.2 M KCI) were followed fluorimetrically and evaluated kinetically. The study was completed with a theoretical analysis based on the inverse of the Fukui potential (1/v(f) (r)), which is proposed for the first time as a local softness descriptor. Thus, considering both experimental results and theoretical analysis, the following conclusions can be drawn: (i) the reactivity of the tested probes towards Michael addition increases in the para-substitution sequence: H < OEt < SMe < Br < NO2, and is not correlated with the sigma(P) values of the substituents; (ii) in turn, the descriptor proposed here as local softness (1/v(f) (r)) appears as a promising reactivity index that is able to explain the higher k(N) values found for both electron-withdrawing and electron-donating groups; (iii) the nucleophilic reactivity of the biothiols employed increases in the sequence Cys-Gly < Hcy < GSH < Cys < gamma-Glu-Cys; and also finally (iv) we have demonstrated that these probes can be used for fluorimetric thiol determination in SH-SY5Y cells.}, keywords = {alpha, beta-unsaturated chemical-reactivity, cysteine, density-functional-approach, disease, electrophilicity fluorescent, glutathione, ketones, michael probe, turn-on}, pubstate = {published}, tppubtype = {article} } The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, gamma-glutamylcysteine and glutathione with 3-cinnamoylcoumarin derivatives (ChC1-ChC4) in aqueous solution (30 degrees C, ionic strength 0.2 M KCI) were followed fluorimetrically and evaluated kinetically. The study was completed with a theoretical analysis based on the inverse of the Fukui potential (1/v(f) (r)), which is proposed for the first time as a local softness descriptor. Thus, considering both experimental results and theoretical analysis, the following conclusions can be drawn: (i) the reactivity of the tested probes towards Michael addition increases in the para-substitution sequence: H < OEt < SMe < Br < NO2, and is not correlated with the sigma(P) values of the substituents; (ii) in turn, the descriptor proposed here as local softness (1/v(f) (r)) appears as a promising reactivity index that is able to explain the higher k(N) values found for both electron-withdrawing and electron-donating groups; (iii) the nucleophilic reactivity of the biothiols employed increases in the sequence Cys-Gly < Hcy < GSH < Cys < gamma-Glu-Cys; and also finally (iv) we have demonstrated that these probes can be used for fluorimetric thiol determination in SH-SY5Y cells. |
2016 |
Gastroprotective Activity of Synthetic Coumarins: Role of Endogenous Prostaglandins, Nitric Oxide, Non-Protein Sulfhydryls and Vanilloid Receptors Artículo de revista Bioorganic & Medicinal Chemistry Letters, 26 (23), pp. 5732-5735, 2016, ISSN: 0960-894x. |
2014 |
Substituent Effects on Reactivity of 3-Cinnamoylcoumarins with Thiols of Biological Interest Artículo de revista Rsc Advances, 4 (2), pp. 697-704, 2014, ISSN: 2046-2069. |