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Research Project
Strategic Project - LA 6 - 2011-2012
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Publications
Autohydrolysis of Annona cherimola Mill. seeds: optimization, modeling and products characterization
Publication . Branco, P. C.; Dionísio, A.M.; Torrado, I.; Carvalheiro, F.; Castilho, P. C.; Duarte, L.C.
Annona cherimola Mill. seeds are a residue of the industrial processing of this fruit, for which, presently,
there is no industrial application. They have a considerable amount of oil, which can be converted into
biodiesel, but the remaining lignocellulosic fraction still needs relevant added-value valorization routes.
Inthis work,the selectivehemicelluloses removal by autohydrolysis was optimizedaiming tomaximize
the yield of oligosaccharides with potential applications in food, pharmaceutical and cosmetic industries.
A maximum of 10.4 g L−1 of oligosaccharides was obtained, for a severity factor of 3.6, where 74.5% of the
original hemicellulose was solubilized.
The process kinetics is presented, modeled (based on the Arrhenius equation) and its scale-up is dis cussed. The hydrolyzate shelf-life was evaluated and the produced oligosaccharides are stable at room
temperature for, at least, 3 weeks. Furthermore, all oligosaccharides are also stable at 100 ◦C for 1 h, in pH
values between 1 and 11, enabling their industrial processing, and at 37 ◦C for 3 h, in pH values between
1 and 3, thus indicating its potential classification as non-digestible oligosaccharides. The remaining cel lulose enriched solids presented an increased enzymatic digestibility (as a function of the autohydrolysis
severity) that assures its efficient use in subsequent processes (e.g., bioethanol production).
The upgrade route developed in this work in combination to the previously reported use of A. cherimola
seed oil for biodiesel production can lead to an integrated zero-waste valorization strategy within the
biorefinery framework.
Discovery of a new small-molecule inhibitor of p53–MDM2 interaction using a yeast-based approach
Publication . Leão, Mariana; Pereira, Clara; Bisio, Alessandra; Ciribilli, Yari; Paiva, Ana M.; Machado, Neuza; Palmeira, Andreia; Fernandes, Miguel X.; Sousa, Emília; Pinto, Madalena; Inga, Alberto; Saraiva, Lucília
The virtual screening of a library of xanthone derivatives led us to the identification of potential novel
MDM2 ligands. The activity of these compounds as inhibitors of p53–MDM2 interaction was
investigated using a yeast phenotypic assay, herein developed for the initial screening. Using this
approach, in association with a yeast p53 transactivation assay, the pyranoxanthone (3,4-dihydro-12-
hydroxy-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one) (1) was identified as a putative small molecule inhibitor of p53–MDM2 interaction.
The activity of the pyranoxanthone 1 as inhibitor of p53–MDM2 interaction was further investigated
in human tumor cells with wild-type p53 and overexpressed MDM2. Notably, the pyranoxanthone 1
mimicked the activity of known p53 activators, leading to p53 stabilization and activation of p53-
dependent transcriptional activity. Additionally, it led to increased protein levels of p21 and Bax, and to
caspase-7 cleavage. By computational docking studies, it was predicted that, like nutlin-3a, a known
small-molecule inhibitor of p53–MDM2 interaction, pyranoxanthone 1 binds to the p53-binding site of
MDM2.
Overall, in this work, a novel small-molecule inhibitor of p53–MDM2 interaction with a xanthone
scaffold was identified for the first time. Besides its potential use as molecular probe and possible lead to
develop anticancer agents, the pyranoxanthone 1 will pave the way for the structure-based design of a
new class of p53–MDM2 inhibitors.
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Funders
Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
6820 - DCRRNI ID
Funding Award Number
PEst-C/EQB/LA0006/2011