129 research outputs found
Synthesis and in vitro α-glucosidase inhibitory activity of polyhydroxylated 2-styrylchromones
2-Styrylchromones (2-SC) are a small class of naturally-occurring oxygen-containing heterocycles. Although
they are scarce in nature, a large number of 2-SC derivatives has been synthesized and their biological activ ity
evaluated, namely as antiallergic, anti-inflammatory, antimicrobial, antioxidant and antitumor agents [l]. As far
as we know, the antidiabetic activity of 2-SC is still unexplored. With this rational in mind, a series of 12
polyhydroxylated derivatives of 2-SC (1) were synthethized and used as inhibitors of the carbohydrate
hydrolyzing enzyme a-glucosidase. This enzyme catalyzes the final step of the digestive process of starch and
break down oligosaccharides to monosaccharides being one of the most currently used therapeutic approaches to
decrease postprandial hyperglycemia and consequently to control type 2 diabetes mellitus [2].
The synthesis of polyhydroxylated 2-SC involves a multi-step strategy starting with the condensation of the
appropriate 2'-hydroxyacetophenones with cinnamic acid derivatives, base-promoted Baker- Yenkataraman
rearrangement of the esters formed, cyclodehydration and finnaly cleavage of the protecting groups to afford the
desired polyhydroxylated 2-SC (3]. The in vitro assay to evaluate the inhibitory activity of the compounds under
study and the positive control, acarbose, against a-glucosidase was performed by monitoring the hydrolysis of
the substrate p-nitrophenyl glucopyranoside into the product p-nitrophenol at 405 nm. In addition, the study of
the inhibition type was carried out through nonlinear regression Michaelis-Menton enzymatic kinetics and the
corresponding Lineweaver-Burk plot [4].This work received financial support from the European Union (FEDER funds
POCI/01 /0145/FEDER/007265) and National Funds (FCT/MEC, Fundayiio para a Ciencia e Tecnologia and
Ministerio da Educação e Ciência) under the Partnership Agreement PT2020 UID/ AGR/00690/2013;
UID/QUI/50006/2013; UID/QUI/00062/2019, and "Programa Operacional Competitividade e
Intemacionalizayiio" (COMPETE) (POCI-01-0145-FEDER-029241), and under the framework of QREN
(NORTE-01-0145-FEDER-000024).info:eu-repo/semantics/publishedVersio
Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones
Xanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and
pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic
profile, mainly as α-glucosidase inhibitors. However, studies concerning the inhibition of both
carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase are scarce. Thus, in order to identify
some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated
together with their commercial parents mangiferin (4), α-mangostin (5) and γ-mangostin (6). The results
showed that xanthones exhibited a systematic stronger inhibition against α-glucosidase rather than for
α-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of
α-amylase, while xanthones 2c, 3b and 3c were the most active against α-glucosidase activity, with IC50
values lower than 10 μM. These findings suggest that the substitution pattern of the xanthone scaffold
modulated the inhibitory activity of these compounds, and some structure–activity relationships could be
established for both assays. In addition, the type of inhibition was also studied, and the results indicate a
competitive type of inhibition for α-amylase activity by xanthones 2c, 3b, 3c and γ-mangostin (6). On the
other hand, non-competitive inhibition mechanisms can be ascribed for all xanthones 1–6 against
α-glucosidase. The present work can open a promising area of research based on the design of novel
xanthone derivatives, based on natural ones, for targeting key enzymes involved in glucose metabolism
and therefore in the management of type 2 diabetes mellitus.The work was supported by UIBD/00690/2020 and UIDB/50006/2020 with funding from FCT/MCTES through national
funds, and by EXPL/MED-QUI/0815/2021, with funding from FCT. Carina Proença acknowledges funding from FCT and
MCTES through national funds and COMPETE, grant number PTDC/MED-QUI/29243/2017 -POCI-01-0145-FEDER-029243.
Marisa Freitas acknowledges her contract under the Scientific Employment Stimulus - Individual Call (CEEC Individual)
2020.04126.CEECIND/CP1596/CT0006.info:eu-repo/semantics/publishedVersio
2-Styrylchromones as inhibitors of α-amylase and α-glucosidase enzymes for the management of type 2 diabetes mellitus
alpha-amylase and alpha-glucosidase are key enzymes implicated in carbohydrate digestion and their inhibition has been suggested as a powerful approach for regulating blood glucose levels. The present work describes for the first time their inhibition by a group of twelve hydroxylated 2-styrylchromones (2-SC). Our findings revealed that 2-SC display strong systematic inhibition of alpha-glucosidase rather than alpha-amylase activity. The number and position of the hydroxy groups in the chromone moiety further modulate the inhibitory profile of the studied compounds, and the derivatives bearing one catechol unit are efficient inhibitors of both enzymes. Enzyme kinetic studies indicate that all active compounds act as competitive inhibitors of alpha-amylase while most of them behave as non-competitive inhibitors of alpha-glucosidase. The results are promising and pave the way to further deciphering the potential of this class of compounds as a suitable alternative for the management of type 2 diabetes and its complications.This work received support from national funds (FCT/
MCTES, Fundação para a Ciência e Tecnologia and Ministério da
Ciência, Tecnologia e Ensino Superior) through the projects of CIMO
(UIDB/00690/2020 and), SusTEC (LA/P/0007/2021) and
REQUIMTE (UIDB/50006/2020 and UIDP/50006/2020). This work
also received financial support from the project EXPL/MED-QUI/
0815/2021, with funding from FCT/MCTES through national funds,
and “Programa Operacional Competitividade e Internacionalização”
(COMPETE). Open access funding provided by FCT|FCCN (b-on).info:eu-repo/semantics/publishedVersio
A study towards drug discovery for the management of type 2 diabetes: Mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives
The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major
therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for
their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the
present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo
substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first
time. The results showed that the substitution patterns and the type of substituents of chalcones
influence their inhibitory activity. The presence of hydroxy groups at C-2’- and C-4’ of the A ring and at
C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents,
together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the
α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the
design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.This work received financial support from the European Union
(FEDER funds POCI/01/0145/FEDER/007265) and National
Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and
Ministério da Educação e Ciência) under the Partnership
Agreement PT2020 UID/QUI/50006/2013, and “Programa
Operacional Competitividade e Internacionalização” (COMPETE) (POCI-01-0145-FEDER-029241). Thanks are due to University of Aveiro, Instituto Politécnico de Bragança, FCT/
MEC for the financial support to the QOPNA (FCT UID/QUI/
00062/2013) and CIMO (UID/AGR/00690/2013) research Units
through national funds and where applicable co-financed by
the FEDER, within the PT2020 Partnership Agreement, and
also to the Portuguese NMR Network. Sónia Rocha acknowledges
FCT the financial support for the PhD grant (PD/BD/
145169/2019), in the ambit of “QREN – POPH – Tipologia 4.1 –
Formação Avançada”, co-sponsored by Fundo Social Europeu
(FSE) and by national funds of Ministério da Ciência,
Tecnologia e Ensino Superior (MCTES).info:eu-repo/semantics/publishedVersio
Atmospheric particulate matter from an industrial area as a source of metal nanoparticle contamination in aquatic ecosystems
Air pollution legislation and control worldwide is based on the size of particulate matter (PM) to evaluate the effects on environmental and human health, in which the small diameter particles are considered more dangerous than larger sizes. This study investigates the composition, stability, size and dispersion of atmospheric settleable particulate matter (SePM) in an aqueous system. We aimed to interrogate the changes in the physical properties and characteristics that can contribute to increased metal uptake by aquatic biota. Samples collected in an area influenced by the steel and iron industry were separated into 8 fractions (425 to ≤10 μm) and analysed physically and chemically. Results from ICP-MS and X-ray showed that the PM composition was mainly hematite with 80% of Fe, followed by Al, Mn and Ti. Among 27 elements analysed we found 19 metals, showing emerging metallic contaminants such as Y, Zr, Sn, La, Ba and Bi. Scanning electron microscopy (SEM) showed that SePM fractions are formed by an agglomeration of nanoparticles. Furthermore, dynamic light scattering (DLS), zeta potential and nanoparticle tracking analysis (NTA) demonstrated that SPM were dissociated in water, forming nanoparticles smaller than 200 nm, which can also contribute to water pollution. This study highlights that SePM contamination may be substantially higher than expected under that allowed in atmospheric regulatory frameworks, thereby extending their negative effect to water bodies upon settling, which is an underexplored area of our knowledge. We therefore provide important insights for future investigations on safety regulations involving SePM in the environment, indicating the need to revise the role of SePM, not solely associated with air pollution but also considering their deleterious effects on water resources
Innovation for resilience
Last decade is characterized by different types of crises and shocs in the socioeconomic systems, creating a turbulent context and calling for a better understanding of what the dynamic perspective of change is. For countries, regions and cities a better understanding of governance urges and calls for action
Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017
Background
Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout.
Methods
The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function.
Findings
Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function.
Interpretation
Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI
Early holocenic and historic mtDNA african signatures in the iberian peninsula: The andalusian region as a paradigm
Determining the timing, identity and direction of migrations in the Mediterranean Basin, the role of "migratory routes" in and among regions of Africa, Europe and Asia, and the effects of sex-specific behaviors of population movements have important implications for our understanding of the present human genetic diversity. A crucial component of the Mediterranean world is its westernmost region. Clear features of transcontinental ancient contacts between North African and Iberian populations surrounding the maritime region of Gibraltar Strait have been identified from archeological data. The attempt to discern origin and dates of migration between close geographically related regions has been a challenge in the field of uniparental-based population genetics. Mitochondrial DNA (mtDNA) studies have been focused on surveying the H1, H3 and V lineages when trying to ascertain north-south migrations, and U6 and L in the opposite direction, assuming that those lineages are good proxies for the ancestry of each side of the Mediterranean. To this end, in the present work we have screened entire mtDNA sequences belonging to U6, M1 and L haplogroups in Andalusians--from Huelva and Granada provinces--and Moroccan Berbers. We present here pioneer data and interpretations on the role of NW Africa and the Iberian Peninsula regarding the time of origin, number of founders and expansion directions of these specific markers. The estimated entrance of the North African U6 lineages into Iberia at 10 ky correlates well with other L African clades, indicating that U6 and some L lineages moved together from Africa to Iberia in the Early Holocene. Still, founder analysis highlights that the high sharing of lineages between North Africa and Iberia results from a complex process continued through time, impairing simplistic interpretations. In particular, our work supports the existence of an ancient, frequently denied, bridge connecting the Maghreb and Andalusia.Financial support was provided by the Spanish Ministry of Competitiveness through Research Project CGL2010-15191/BOS granted to RC and International Mobility Program Acciones Integradas Hispano-Portuguesas (PRI-AIBPT-2011-1004) granted to RC (Spain) and LP (Portugal) (http://www.mineco.gob.es/portal/site/mineco/idi). The E.C. Sixth Framework Programme under Contract n° ERAS-CT-2003-980409 (EUROCORES project of the European Science Foundation) also provided financial support to JMD for North African population research. CLH has a predoctoral fellowship granted by Complutense University. PS is supported by FCT Investigator Programme (IF/01641/2013). IPATIMUP (https://www.ipatimup.pt/) integrates the Instituto the Investigação em Saúde (i3S) Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. IPATIMUP is funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE and National Funds through the FCT - under the project PEst-C/SAU/LA0003/2013. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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