New highly hydrosoluble and not self-aggregated perylene derivatives with three and four polar side-chains as G-quadruplex telomere targeting agents and telomerase inhibitors.
Four new perylene derivatives with three and four basic side-chains are reported here as G-quadruplex interactive compounds. The new perylene derivatives are readily soluble in water and not self-aggregated, in contrast to what happens with the previously reported two side-chain perylene derivatives. All four compounds are able to induce the G-quadruplex and to inhibit 50% of telomerase activity at about 5 microM concentration, showing a similar efficiency with respect to each other. Molecular modelling studies are presented to try to explain these findings.
Franceschin
Marco
M
Dipartimento di Chimica, Università di Roma La Sapienza, Piazzale A. Moro 5, 00185 Roma, Italy. marco.franceschin@uniroma1.it
Pascucci
Emanuela
E
Alvino
Antonello
A
D'Ambrosio
Danilo
D
Bianco
Armandodoriano
A
Ortaggi
Giancarlo
G
Savino
Maria
M
D002626:Chemistry, Pharmaceutical / Q000379:methods; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D010569:Perylene / Q000031:analogs & derivatives / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000737:chemistry*
D004791:Enzyme Inhibitors; D010569:Perylene; D004247:DNA; D019098:Telomerase