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 IC50values 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.

Camptothecin-psammaplin A hybrids as topoisomerase I and HDAC dual-action inhibitors / R. Cincinelli, L. Musso, R. Artali, M. Guglielmi, E. Bianchino, F. Cardile, F. Colelli, C. Pisano, S. Dallavalle. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 143(2018), pp. 2005-2014.

Camptothecin-psammaplin A hybrids as topoisomerase I and HDAC dual-action inhibitors

R. Cincinelli;L. Musso;S. Dallavalle
2018

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 IC50values 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.
Psammaplin; HDAC inhibitors; Camptothecin; Antiproliferative activity; Antitumor activity; Dual-action inhibitors
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/06 - Chimica Organica
8-nov-2017
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/544983
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