Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents

Recent studies have shown that HDAC inhibitors act synergistically with camptothecin derivatives in combination therapies. To exploit this synergy, new hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothe...

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Autores principales: Cincinelli, Raffaella, Musso, Loana, Artali, Roberto, Guglielmi, Mario B., La Porta, Ilaria, Melito, Carmela, Colelli, Fabiana, Cardile, Francesco, Signorino, Giacomo, Fucci, Alessandra, Frusciante, Martina, Pisano, Claudio, Dallavalle, Sabrina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177136/
https://www.ncbi.nlm.nih.gov/pubmed/30300374
http://dx.doi.org/10.1371/journal.pone.0205018
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author Cincinelli, Raffaella
Musso, Loana
Artali, Roberto
Guglielmi, Mario B.
La Porta, Ilaria
Melito, Carmela
Colelli, Fabiana
Cardile, Francesco
Signorino, Giacomo
Fucci, Alessandra
Frusciante, Martina
Pisano, Claudio
Dallavalle, Sabrina
author_facet Cincinelli, Raffaella
Musso, Loana
Artali, Roberto
Guglielmi, Mario B.
La Porta, Ilaria
Melito, Carmela
Colelli, Fabiana
Cardile, Francesco
Signorino, Giacomo
Fucci, Alessandra
Frusciante, Martina
Pisano, Claudio
Dallavalle, Sabrina
author_sort Cincinelli, Raffaella
collection PubMed
description Recent studies have shown that HDAC inhibitors act synergistically with camptothecin derivatives in combination therapies. To exploit this synergy, new hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothecin and a SAHA-like template showed a broad spectrum of antiproliferative activity, with IC(50) values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability.
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spelling pubmed-61771362018-10-19 Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents Cincinelli, Raffaella Musso, Loana Artali, Roberto Guglielmi, Mario B. La Porta, Ilaria Melito, Carmela Colelli, Fabiana Cardile, Francesco Signorino, Giacomo Fucci, Alessandra Frusciante, Martina Pisano, Claudio Dallavalle, Sabrina PLoS One Research Article Recent studies have shown that HDAC inhibitors act synergistically with camptothecin derivatives in combination therapies. To exploit this synergy, new hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothecin and a SAHA-like template showed a broad spectrum of antiproliferative activity, with IC(50) values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability. Public Library of Science 2018-10-09 /pmc/articles/PMC6177136/ /pubmed/30300374 http://dx.doi.org/10.1371/journal.pone.0205018 Text en © 2018 Cincinelli et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cincinelli, Raffaella
Musso, Loana
Artali, Roberto
Guglielmi, Mario B.
La Porta, Ilaria
Melito, Carmela
Colelli, Fabiana
Cardile, Francesco
Signorino, Giacomo
Fucci, Alessandra
Frusciante, Martina
Pisano, Claudio
Dallavalle, Sabrina
Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
title Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
title_full Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
title_fullStr Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
title_full_unstemmed Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
title_short Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
title_sort hybrid topoisomerase i and hdac inhibitors as dual action anticancer agents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177136/
https://www.ncbi.nlm.nih.gov/pubmed/30300374
http://dx.doi.org/10.1371/journal.pone.0205018
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