Strategic Project - LA 6 - 2011-2012

Funder

Organizational Unit

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.

2015Journal article

Open access

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.

2013Journal article

Open access