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

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., Dömling, A. & Spanu, P., 13-Oct-2016, In : Journal of Medicinal Chemistry. 59, 19, p. 9140-9149 10 p.

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DOI

  • 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
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.
Original languageEnglish
Pages (from-to)9140-9149
Number of pages10
JournalJournal of Medicinal Chemistry
Volume59
Issue number19
Publication statusPublished - 13-Oct-2016

    Keywords

  • 2 (furan 2 yl) 6 methyltetrahydro 2h pyran 2 ol, 2 hydroxy 8 methyl 1,7 dioxaspiro[5.5]undec 3 en 5 one, antineoplastic agent, guanine quadruplex, spiro compound, telomerase inhibitor, unclassified drug, antineoplastic activity, antiproliferative activity, apoptosis, article, cell proliferation assay, circular dichroism, controlled study, diastereoisomer, drug synthesis, enantiomer, HL 60 cell line, HT 29 cell line, human, human cell, in vitro study, MCF 7 cell line, molecular docking, stereoisomerism, thermostability

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