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

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.