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.

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

Mannu A.;
2016-01-01

Abstract

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.
2016
59
19
9140
9149
Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Enzyme Inhibitors; Furans; G-Quadruplexes; Humans; Models, Molecular; Molecular Docking Simulation; Neoplasms; Spiro Compounds; Stereoisomerism; Structure-Activity Relationship; Telomerase
Fuggetta M.P.; De Mico A.; Cottarelli A.; Morelli F.; Zonfrillo M.; Ulgheri F.; Peluso P.; Mannu A.; Deligia F.; Marchetti M.; Roviello G.; Reyes Romero A.; Domling A.; Spanu P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1735712
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