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 et al. · PLoS One · 2018

basic_science · Level V

Where this comes from

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.

Medical subject headings