2018 |
Fuentes-Barros, G; Castro-Saavedra, S; Liberona, L; Acevedo-Fuentes, W; Tirapegui, C; Mattar, C; Cassels, B K Variation of the Alkaloid Content of Peumus Boldus (Boldo) Artículo de revista Fitoterapia, 127 , pp. 179-185, 2018, ISSN: 0367-326x. Resumen | Enlaces | BibTeX | Etiquetas: activity, alkaloids, antioxidant boldine, boldus, herbal in-vitro, inhibition, leaves, medicine, peumus peumus-boldus, phenanthrene phytochemistry, plants, products, reticuline traditional uhplc-ms/ms @article{RN386, title = {Variation of the Alkaloid Content of Peumus Boldus (Boldo)}, author = { G. Fuentes-Barros and S. Castro-Saavedra and L. Liberona and W. Acevedo-Fuentes and C. Tirapegui and C. Mattar and B.K. Cassels}, url = {/brokenurl#<Go to ISI>://WOS:000437551000027}, doi = {10.1016/j.fitote.2018.02.020}, issn = {0367-326x}, year = {2018}, date = {2018-01-01}, journal = {Fitoterapia}, volume = {127}, pages = {179-185}, abstract = {Eighteen alkaloids were detected in the bark, leaves, wood and roots of Peumus boldus, including traces of secoboldine, N-methylsecoboldine (boldine methine), glaucine and norreticuline, not reported previously as constituents of this species. Using appropriate standards, we quantified thirteen of them by UHPLC-MS/MS. Boldine was dominant in the bark, and laurolitsine in wood and roots. The alkaloid composition of the leaves, determined for 130 individually identified trees, classified by age and sex, was highly variable, where N-methyllaurotetanine, laurotetanine, coclaurine and in some cases isocorydine predominated, but not boldine.}, keywords = {activity, alkaloids, antioxidant boldine, boldus, herbal in-vitro, inhibition, leaves, medicine, peumus peumus-boldus, phenanthrene phytochemistry, plants, products, reticuline traditional uhplc-ms/ms}, pubstate = {published}, tppubtype = {article} } Eighteen alkaloids were detected in the bark, leaves, wood and roots of Peumus boldus, including traces of secoboldine, N-methylsecoboldine (boldine methine), glaucine and norreticuline, not reported previously as constituents of this species. Using appropriate standards, we quantified thirteen of them by UHPLC-MS/MS. Boldine was dominant in the bark, and laurolitsine in wood and roots. The alkaloid composition of the leaves, determined for 130 individually identified trees, classified by age and sex, was highly variable, where N-methyllaurotetanine, laurotetanine, coclaurine and in some cases isocorydine predominated, but not boldine. |
Villalobos, V; Leiva, A; Rios, H; Pavez, J; Silva, C P; Ahmar, M; Queneau, Y; Blamey, J M; Chavez, F P; Urzúa, M Inhibiting Pathogen Surface Adherence by Multilayer Polyelectrolyte Films Functionalized with Glucofuranose Derivatives Artículo de revista Acs Applied Materials & Interfaces, 10 (33), pp. 28147-28158, 2018, ISSN: 1944-8244. Resumen | Enlaces | BibTeX | Etiquetas: antibacterial bacterial, biofilm biomaterials, carbohydrate challenges coatings, construction, formation, inhibition, mechanisms, p. polyelectrolytes, resistance, s. surfaces, typhimurium @article{RN403, title = {Inhibiting Pathogen Surface Adherence by Multilayer Polyelectrolyte Films Functionalized with Glucofuranose Derivatives}, author = { V. Villalobos and A. Leiva and H. Rios and J. Pavez and C.P. Silva and M. Ahmar and Y. Queneau and J.M. Blamey and F.P. Chavez and M. Urz\'{u}a}, url = {/brokenurl#<Go to ISI>://WOS:000442706600064}, doi = {10.1021/acsami.8b03605}, issn = {1944-8244}, year = {2018}, date = {2018-01-01}, journal = {Acs Applied Materials & Interfaces}, volume = {10}, number = {33}, pages = {28147-28158}, abstract = {Inhibiting pathogenic bacterial adherence on surfaces is an ongoing challenge to prevent the development of biofilms. Multilayer polyelectrolyte films are feasible antibacterial materials. Here, we have designed new films made of carbohydrate polyelectrolytes to obtain antibacterial coatings that prevent biofilm formation. The polyelectrolyte films were constructed from poly(maleic anhydride-alt-styrene) functionalized with glucofuranose derivatives and quaternized poly(4-vinylpyridine) N-alkyl. These films prevent Pseudomonas aeruginosa and Salmonella Typhimurium, two important bacterial contaminants in clinical environments, from adhering to surfaces. When the film was composed of more than 10 layers, the bacterial population was greatly reduced, while the bacteria remaining on the film were morphologically damaged, as atomic force microscopy revealed. The antibacterial capacity of the polyelectrolyte films was determined by the combination of thickness, wettability, surface energy, and most importantly, the conformation that polyelectrolytes adopt the function of nature of the carbohydrate group. This polyelectrolyte film constitutes the first green approach to preventing pathogenic bacterial surface adherence and proliferation without killing the bacterial pathogen.}, keywords = {antibacterial bacterial, biofilm biomaterials, carbohydrate challenges coatings, construction, formation, inhibition, mechanisms, p. polyelectrolytes, resistance, s. surfaces, typhimurium}, pubstate = {published}, tppubtype = {article} } Inhibiting pathogenic bacterial adherence on surfaces is an ongoing challenge to prevent the development of biofilms. Multilayer polyelectrolyte films are feasible antibacterial materials. Here, we have designed new films made of carbohydrate polyelectrolytes to obtain antibacterial coatings that prevent biofilm formation. The polyelectrolyte films were constructed from poly(maleic anhydride-alt-styrene) functionalized with glucofuranose derivatives and quaternized poly(4-vinylpyridine) N-alkyl. These films prevent Pseudomonas aeruginosa and Salmonella Typhimurium, two important bacterial contaminants in clinical environments, from adhering to surfaces. When the film was composed of more than 10 layers, the bacterial population was greatly reduced, while the bacteria remaining on the film were morphologically damaged, as atomic force microscopy revealed. The antibacterial capacity of the polyelectrolyte films was determined by the combination of thickness, wettability, surface energy, and most importantly, the conformation that polyelectrolytes adopt the function of nature of the carbohydrate group. This polyelectrolyte film constitutes the first green approach to preventing pathogenic bacterial surface adherence and proliferation without killing the bacterial pathogen. |
Noureini, S K; Kheirabadi, M; Masoumi, F; Khosrogerdi, F; Zarei, Y; Suarez-Rozas, C; Salas-Norambuena, J; Cassels, B K Telomerase Inhibition by a New Synthetic Derivative of the Aporphine Alkaloid Boldine Artículo de revista International Journal of Molecular Sciences, 19 (4), 2018, ISSN: 1422-0067. Resumen | Enlaces | BibTeX | Etiquetas: apoptosis, assay binding boldine, cells, derivative, domain, inhibition, n-benzylsecoboldine, site, stress, telomerase @article{RN387, title = {Telomerase Inhibition by a New Synthetic Derivative of the Aporphine Alkaloid Boldine}, author = { S.K. Noureini and M. Kheirabadi and F. Masoumi and F. Khosrogerdi and Y. Zarei and C. Suarez-Rozas and J. Salas-Norambuena and B.K. Cassels}, url = {/brokenurl#<Go to ISI>://WOS:000434978700318}, doi = {10.3390/ijms19041239}, issn = {1422-0067}, year = {2018}, date = {2018-01-01}, journal = {International Journal of Molecular Sciences}, volume = {19}, number = {4}, abstract = {Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC50 value of about 0.17 +/- 0.1 mu M for BSB, roughly 400 times stronger than boldine, while the LD50 in the cytotoxicity assays were 12.5 and 21.88 mu M, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC50 for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations.}, keywords = {apoptosis, assay binding boldine, cells, derivative, domain, inhibition, n-benzylsecoboldine, site, stress, telomerase}, pubstate = {published}, tppubtype = {article} } Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC50 value of about 0.17 +/- 0.1 mu M for BSB, roughly 400 times stronger than boldine, while the LD50 in the cytotoxicity assays were 12.5 and 21.88 mu M, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC50 for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations. |
2017 |
Cornejo, A; Sandoval, F A; Caballero, L; Machuca, L; Munoz, P; Caballero, J; Perry, G; Ardiles, A; Areche, C; Melo, F Rosmarinic Acid Prevents Fibrillization and Diminishes Vibrational Modes Associated to Beta Sheet in Tau Protein Linked to Alzheimer's Disease Artículo de revista Journal of Enzyme Inhibition and Medicinal Chemistry, 32 (1), pp. 945-953, 2017, ISSN: 1475-6366. Resumen | Enlaces | BibTeX | Etiquetas: alzheimer's amyloid beta-sheet, carnosic cells criteria, disease, fibril filaments, formation, helical in-vitro, inhibition, inhibitors, mice, neuropathologic paired pharmacophore, salvia-officinalis, tau transgenic @article{RN337, title = {Rosmarinic Acid Prevents Fibrillization and Diminishes Vibrational Modes Associated to Beta Sheet in Tau Protein Linked to Alzheimer's Disease}, author = { A. Cornejo and F.A. Sandoval and L. Caballero and L. Machuca and P. Munoz and J. Caballero and G. Perry and A. Ardiles and C. Areche and F. Melo}, url = {/brokenurl#<Go to ISI>://WOS:000406130000006}, doi = {10.1080/14756366.2017.1347783}, issn = {1475-6366}, year = {2017}, date = {2017-01-01}, journal = {Journal of Enzyme Inhibition and Medicinal Chemistry}, volume = {32}, number = {1}, pages = {945-953}, abstract = {Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-beta plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents beta-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and beta sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid.}, keywords = {alzheimer's amyloid beta-sheet, carnosic cells criteria, disease, fibril filaments, formation, helical in-vitro, inhibition, inhibitors, mice, neuropathologic paired pharmacophore, salvia-officinalis, tau transgenic}, pubstate = {published}, tppubtype = {article} } Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-beta plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents beta-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and beta sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid. |
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. |
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