Synthesis and Enantiomeric Separation of a Novel Spiroketal Derivative: A Potent Human Telomerase Inhibitor with High in Vitro Anticancer Activity

Maria Pia Fuggetta, Antonella De Mico, Andrea Cottarelli, Franco Morelli, Manuela Zonfrillo, Fausta Ulgheri, Paola Peluso, Alberto Mannu, Francesco Deligia, Mauro Marchetti, Giovanni Roviello, Atilio Reyes Romero, Alexander Dömling, Pietro Spanu

OnderzoeksoutputAcademicpeer review

7 Citaten (Scopus)
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Samenvatting

The synthesis, the enantiomeric separation, and the characterization of new simple spiroketal derivatives have been performed. The synthesized compounds have shown a very high anticancer activity. Cell proliferation assay showed that they induce a remarkable inhibition of cell proliferation in all cell lines treated, depending on culture time and concentration. The compounds have also shown a potent nanomolar human telomerase inhibition activity and apoptosis induction. CD melting experiments demonstrate that spiroketal does not affect the G-quadruplex (G4) thermal stability. Docking studies showed that telomerase inhibition could be determined by a spiroketal interaction with the telomerase enzyme.
Originele taal-2English
Pagina's (van-tot)9140-9149
Aantal pagina's10
TijdschriftJournal of Medicinal Chemistry
Volume59
Nummer van het tijdschrift19
DOI's
StatusPublished - 13-okt-2016

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