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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Detalles Bibliográficos
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
Descripción
Sumario: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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