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 IC50 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.
Hybrid topoisomerase i and HDAC inhibitors as dual action anticancer agents / R. Cincinelli, L. Musso, R. Artali, M.B. Guglielmi, I. La Porta, C. Melito, F. Colelli, F. Cardile, G. Signorino, A. Fucci, M. Frusciante, C. Pisano, S. Dallavalle. - In: PLOS ONE. - ISSN 1932-6203. - 13:10(2018 Oct).
Hybrid topoisomerase i and HDAC inhibitors as dual action anticancer agents
R. CincinelliPrimo
;L. MussoSecondo
;S. Dallavalle
Ultimo
2018
Abstract
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 IC50 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.File | Dimensione | Formato | |
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