title: Catecholic flavonoids acting as telomerase inhibitors.
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.
authors.affiliation: Department of Chemistry, BU-Nerviano Medical Sciences, Viale Pasteur 10, 20014 Nerviano (MI), Italy. maria.menichincheri@nervianoms.com
authors.forename: Maria
authors.initials: M
authors.lastname: Menichincheri
authors.forename: Dario
authors.initials: D
authors.lastname: Ballinari
authors.forename: Alberto
authors.initials: A
authors.lastname: Bargiotti
authors.forename: Luisella
authors.initials: L
authors.lastname: Bonomini
authors.forename: Walter
authors.initials: W
authors.lastname: Ceccarelli
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Alessio
authors.forename: Antonella
authors.initials: A
authors.lastname: Fretta
authors.forename: Juergen
authors.initials: J
authors.lastname: Moll
authors.forename: Paolo
authors.initials: P
authors.lastname: Polucci
authors.forename: Chiara
authors.initials: C
authors.lastname: Soncini
authors.forename: Marcellino
authors.initials: M
authors.lastname: Tibolla
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Trosset
authors.forename: Ermes
authors.initials: E
authors.lastname: Vanotti
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry; D047309:Flavones / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002396:Catechols; D047309:Flavones; D019098:Telomerase