Open AccessHybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
Author(s) -
Raffaella Cincinelli,
Loana Musso,
Roberto Artali,
Mario B. Guglielmi,
Ilaria La Porta,
Carmela Melito,
Fabiana Colelli,
Francesco Cardile,
Giacomo Signorino,
Alessandra Fucci,
Martina Frusciante,
Claudio Pisano,
Sabrina Dallavalle
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205018
Subject(s) - camptothecin , topoisomerase , in vivo , topoisomerase inhibitor , pharmacology , chemistry , cancer research , in vitro , biology , biochemistry , microbiology and biotechnology
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.