title: Specific interactions with intra- and intermolecular G-quadruplex DNA structures by hydrosoluble coronene derivatives: a new class of telomerase inhibitors.
abstract: In developing G-quadruplex interactive telomerase inhibitors two main features have to be taken into account: the hydrophobic interactions with the G-quartet plane and the electrostatic interactions with the negatively charged phosphates of the four grooves. In this paper, we report the synthesis of four hydrosoluble coronene derivatives, which are characterized by a large hydrophobic aromatic core and four orthogonal hydrophilic side chains. We have studied their ability to induce both inter- and intramolecular G-quadruplex structures and found a significant selectivity of all the coronene derivatives for the intramolecular G-quadruplex. The efficiency in inhibiting human telomerase has been evaluated in a cell-free system and the experimental results correlate with the relative affinities of these compounds for the G-quadruplex monomeric structure, as derived by molecular modelling simulations. Thus, the coronene derivatives can be considered as a new class of telomerase inhibitors, although further investigations are surely necessary to fully exploit their features.
authors.affiliation: Dipartimento di Chimica, Università di Roma La Sapienza, Piazzale A. Moro 5, 00185 Roma, Italy. marco.franceschin@uniroma1.it
authors.forename: Marco
authors.initials: M
authors.lastname: Franceschin
authors.forename: Antonello
authors.initials: A
authors.lastname: Alvino
authors.forename: Valentina
authors.initials: V
authors.lastname: Casagrande
authors.forename: Clementina
authors.initials: C
authors.lastname: Mauriello
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pascucci
authors.forename: Maria
authors.initials: M
authors.lastname: Savino
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ortaggi
authors.forename: Armandodoriano
authors.initials: A
authors.lastname: Bianco
mesh_terms: D002474:Cell-Free System; D004247:DNA / Q000378:metabolism*; D054856:G-Quadruplexes; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D012995:Solubility; D055672:Static Electricity; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors
chemical_list: D011083:Polycyclic Compounds; C012256:coronene; D004247:DNA; D019098:Telomerase