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Research Project
Madeira Chemistry Research Centre
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Publications
Morpholino-functionalized phosphorus dendrimers for precision regenerative medicine: osteogenic differentiation of mesenchymal stem cells
Publication . Li, Aijun; Fan, Yu; Cao, Xueyan; Chen, Liang; Wang, Le; Alves, Carla S.; Mignani, Serge; Majoral, Jean Pierre; Tomás, Helena; Shi, Xiangyang
A novel bioactive macromolecule based on morpholino-functiona lized phosphorus dendrimers (generation 2, G2-Mor+
) was devel oped for osteogenic differentiation of mesenchymal stem cells
(MSCs). Interestingly, through in vitro tests, it was shown that G2-
Mor+ dendrimer can strongly promote the transformation of MSCs
into osteoblasts, which implies the potential application of phos phorus de medicine.
Volatomic pattern of breast cancer and cancer-free tissues as a powerful strategy to identify potential biomarkers
Publication . Silva, Catarina; Perestrelo, Rosa; Silva, Pedro; Capelinha, Filipa; Tomás, Helena; Câmara, José S.
Breast cancer (BC), ranked as the fifth amongst all cancers, remains at the top of women’s cancers
worldwide followed by colorectal, lung, cervix, and stomach cancers. The main handicap of most of the
screening/diagnostic methods is based on their low sensitivity and specificity and the invasive behavior
of most sampling procedures. The aim of this study was to establish the volatomic pattern of BC and
cancer-free (CF) tissues (n = 30) from the same patients, as a powerful tool to identify a set of volatile
organic metabolite (VOM) potential BC biomarkers which might be used together or complement with
the traditional BC diagnostics strategies, through the integration of chromatographic data, obtained by
solid-phase microextraction followed by gas chromatography-mass spectrometry (SPME/GC-qMS),
with chemometric tools. A total of four metabolites: limonene, decanoic acid, acetic acid and furfural
presented the highest contribution towards discrimination of BC and CF tissues (VIP > 1, p < 0.05). The
discrimination efficiency and accuracy of BC tissue metabolites was ascertained by ROC curve analysis
that allowed the identification of some metabolites with high sensitivity and specificity. The results
obtained with this approach suggest the possibility of identifying endogenous metabolites as a platform
to find potential BC biomarkers and pave the way to investigate the related metabolomic pathways in
order to improve BC diagnostic tools. Moreover, deeper investigations could unravel novel mechanistic
insights into the disease pathophysiology.
Untargeted urinary 1H NMR-based metabolomic pattern as a potential platform in breast cancer detection
Publication . Silva, Catarina L.; Olival, Ana; Perestrelo, Rosa; Silva, Pedro; Tomás, Helena; Câmara, José S.
: Breast cancer (BC) remains the second leading cause of death among women worldwide.
An emerging approach based on the identification of endogenous metabolites (EMs) and the
establishment of the metabolomic fingerprint of biological fluids constitutes a new frontier in medical
diagnostics and a promising strategy to differentiate cancer patients from healthy individuals. In this
work we aimed to establish the urinary metabolomic patterns from 40 BC patients and 38 healthy
controls (CTL) using proton nuclear magnetic resonance spectroscopy (1H-NMR) as a powerful
approach to identify a set of BC-specific metabolites which might be employed in the diagnosis of
BC. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to a 1H-NMR
processed data matrix. Metabolomic patterns distinguished BC from CTL urine samples, suggesting
a unique metabolite profile for each investigated group. A total of 10 metabolites exhibited the
highest contribution towards discriminating BC patients from healthy controls (variable importance
in projection (VIP) >1, p < 0.05). The discrimination efficiency and accuracy of the urinary EMs were
ascertained by receiver operating characteristic curve (ROC) analysis that allowed the identification
of some metabolites with the highest sensitivities and specificities to discriminate BC patients from
healthy controls (e.g. creatine, glycine, trimethylamine N-oxide, and serine). The metabolomic
pathway analysis indicated several metabolism pathway disruptions, including amino acid and
carbohydrate metabolisms, in BC patients, namely, glycine and butanoate metabolisms. The obtained
results support the high throughput potential of NMR-based urinary metabolomics patterns in
discriminating BC patients from CTL. Further investigations could unravel novel mechanistic
insights into disease pathophysiology, monitor disease recurrence, and predict patient response
towards therapy.
Prediction of terpenoid toxicity based on a quantitative structure–activity relationship model
Publication . Perestrelo, Rosa; Silva, Catarina; Fernandes, Miguel X.; Câmara, José S.
Terpenoids, including monoterpenoids (C10), norisoprenoids (C13), and sesquiterpenoids
(C15), constitute a large group of plant-derived naturally occurring secondary metabolites with
highly diverse chemical structures. A quantitative structure–activity relationship (QSAR) model to
predict terpenoid toxicity and to evaluate the influence of their chemical structures was developed in
this study by assessing in real time the toxicity of 27 terpenoid standards using the Gram-negative
bioluminescent Vibrio fischeri. Under the test conditions, at a concentration of 1 µM, the terpenoids
showed a toxicity level lower than 5%, with the exception of geraniol, citral, (S)-citronellal, geranic
acid, (±)-α-terpinyl acetate, and geranyl acetone. Moreover, the standards tested displayed a
toxicity level higher than 30% at concentrations of 50–100 µM, with the exception of (+)-valencene,
eucalyptol, (+)-borneol, guaiazulene, β-caryophellene, and linalool oxide. Regarding the functional
group, terpenoid toxicity was observed in the following order: alcohol > aldehyde ~ ketone >
ester > hydrocarbons. The CODESSA software was employed to develop QSAR models based on
the correlation of terpenoid toxicity and a pool of descriptors related to each chemical structure.
The QSAR models, based on t-test values, showed that terpenoid toxicity was mainly attributed
to geometric (e.g., asphericity) and electronic (e.g., maximum partial charge for a carbon (C) atom
(Zefirov’s partial charge (PC)) descriptors. Statistically, the most significant overall correlation was the
four-parameter equation with a training coefficient and test coefficient correlation higher than 0.810
and 0.535, respectively, and a square coefficient of cross-validation (Q2
) higher than 0.689. According
to the obtained data, the QSAR models are suitable and rapid tools to predict terpenoid toxicity in a
diversity of food products.
An approach of the Madeira wine chemistry
Publication . Perestrelo, Rosa; Luís, Catarina; Gonçalves, Carolina; Castillo, Mariangie; Câmara, José S.
Madeira wine is a fortified Portuguese wine, which has a crucial impact on the Madeira
Island economy. The particular properties of Madeira wine result from the unique and specific
winemaking and ageing processes that promote the occurrence of chemical reactions among
acids, sugars, alcohols, and polyphenols, which are important to the extraordinary quality of
the wine. These chemical reactions contribute to the appearance of novel compounds and/or the
transformation of others, consequently promoting changes in qualitative and quantitative volatile
and non-volatile composition. The current review comprises an overview of Madeira wines related
to volatile (e.g., terpenes, norisoprenoids, alcohols, esters, fatty acids) and non-volatile composition
(e.g., polyphenols, organic acids, amino acids, biogenic amines, and metals). Moreover, types of
aroma compounds, the contribution of volatile organic compounds (VOCs) to the overall Madeira
wine aroma, the change of their content during the ageing process, as well as the establishment
of the potential ageing markers will also be reviewed. The viability of several analytical methods
(e.g., gas chromatography-mass spectrometry (GC-MS), two-dimensional gas chromatography and
time-of-flight mass spectrometry (GC×GC-ToFMS)) combined with chemometrics tools (e.g., partial
least squares regression (PLS-R), partial least squares discriminant analysis (PLS-DA) was investigated
to establish potential ageing markers to guarantee the Madeira wine authenticity. Acetals, furanic
compounds, and lactones are the chemical families most commonly related with the ageing process.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
6817 - DCRRNI ID
Funding Award Number
UID/QUI/00674/2019