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ID: ALA4251569
Journal: Eur J Med Chem
Title: Camptothecin-psammaplin A hybrids as topoisomerase I and HDAC dual-action inhibitors.
Authors: Cincinelli R, Musso L, Artali R, Guglielmi M, Bianchino E, Cardile F, Colelli F, Pisano C, Dallavalle S.
Abstract: Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of camptothecin derivatives and HDAC inhibitors. To exploit this synergy in a single active compound, we designed new dual-acting multivalent molecules simultaneously targeting topoisomerase I and HDAC. In particular, a selected compound containing a camptothecin and the psammaplin A scaffold 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.
CiteXplore: 29150335