6 research outputs found

    Role of the Symmetry of Multipoint Hydrogen Bonding on Chelate Cooperativity in Supramolecular Macrocyclization Processes

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    This is the accepted version of the following article: Angewandte Chemie International Edition 55.1 (2016): 223-227, which has been published in final form at http://dx.doi.org/10.1002/anie.201508854Herein, we analyze the intrinsic chelate effect that multipoint H-bonding patterns exert on the overall energy of dinucleoside cyclic systems. Our results indicate that the chelate effect is regulated by the symmetry of the H-bonding pattern, and that the effective molarity is reduced by about three orders of magnitude when going from the unsymmetric ADD-DAA or DDA-AAD patterns to the symmetric DAD-ADA patternFunding from the European Union (ERC-Starting Grant 279548) and MINECO (CTQ2011-23659 and CTQ2014-57729-P) is gratefully acknowledge

    The FDA-Approved Antiviral Raltegravir Inhibits Fascin1-Dependent Invasion of Colorectal Tumor Cells In Vitro and In Vivo

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    Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Serrated adenocarcinoma (SAC) has been recently recognized by the WHO as a histological CRC with bad prognosis. Consistent with previous evidence, our group identified Fascin1 as a protein directly related to the invasiveness of tumor cells, overexpressed and positively correlated with worse survival in various carcinomas, including SAC. Therefore, Fascin1 has emerged as an ideal target for cancer treatment. In the present study, virtual screening has been carried out from a library of 9591 compounds, thus identifying the FDA-approved anti-retroviral raltegravir (RAL) as a potential Fascin1 blocker. In vitro and in vivo results show that RAL exhibits Fascin1-binding activity and Fascin1-dependent anti-invasive and anti-metastatic properties against CRC cells both in vitro and in vivo
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