2. Academic Validation
  3. Catecholic flavonoids acting as telomerase inhibitors

Catecholic flavonoids acting as telomerase inhibitors

  • J Med Chem. 2004 Dec 16;47(26):6466-75. doi: 10.1021/jm040810b.
Maria Menichincheri 1,  Dario Ballinari,  Alberto Bargiotti,  Luisella Bonomini,  Walter Ceccarelli,  Roberto D'Alessio,  Antonella Fretta,  Juergen Moll,  Paolo Polucci,  Chiara Soncini,  Marcellino Tibolla,  Jean-Yves Trosset,  Ermes Vanotti
Affiliations

Affiliation

  • 1 Department of Chemistry, BU-Nerviano Medical Sciences, Viale Pasteur 10, 20014 Nerviano (MI), Italy. maria.menichincheri@nervianoms.com
PMID: 15588081 DOI: 10.1021/jm040810b
Abstract

In recent years Telomerase has been identified as a new promising target in oncology and consequently new Telomerase inhibitors have been intensely explored as Anticancer agents. Focused screening of several polyhydroxylated Flavonoids has allowed us to identify 7,8,3',4'-tetrahydroxyflavone 1 as a new Telomerase Inhibitor with an interesting in vitro activity in a Flash-Plate assay (IC50 = 0.2 microM) that has been confirmed in the classical TRAP assay. Starting from this compound, we developed a medicinal chemistry program to optimize our lead, and in particular to replace one of the two catechols with potential bioisosteres. From this study, new structural analogues characterized by submicromolar potencies have been obtained. Their synthesis and biological activity are described.

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