1. Synthesis and Enantiomeric Separation of a Novel Spiroketal Derivative: A Potent Human Telomerase Inhibitor with High in Vitro Anticancer Activity
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Andrea Cottarelli, Atilio Reyes Romero, Fausta Ulgheri, Alexander Dömling, Mauro Marchetti, Maria Pia Fuggetta, Manuela Zonfrillo, Pietro Spanu, Giovanni N. Roviello, Franco Morelli, Alberto Mannu, Francesco Deligia, Antonella De Mico, Paola Peluso, Drug Design, and Medicinal Chemistry and Bioanalysis (MCB)
- Subjects
0301 basic medicine ,Models, Molecular ,SPIROKETALS ,Telomerase ,2 hydroxy 8 methyl 1 ,telomerase inhibitor ,2 hydroxy 8 methyl 1,7 dioxaspiro[5.5]undec 3 en 5 one ,01 natural sciences ,Models ,Neoplasms ,enantiomer ,Drug Discovery ,2 (furan 2 yl) 6 methyltetrahydro 2h pyran 2 ol ,Enzyme Inhibitors ,antineoplastic agent ,cell proliferation assay ,Tumor ,Chemistry ,apoptosis ,article ,enantiomeric separation ,unclassified drug ,Molecular Docking Simulation ,Biochemistry ,Molecular Medicine ,stereoisomerism ,antiproliferative activity ,7 dioxaspiro[5.5]undec 3 en 5 one ,in vitro study ,Stereochemistry ,diastereoisomer ,Stereoisomerism ,Antineoplastic Agents ,antineoplastic activity ,G-quadruplex ,anticancer ,HT 29 cell line ,Cell Line ,03 medical and health sciences ,Structure-Activity Relationship ,Cell Line, Tumor ,Structure–activity relationship ,Humans ,Spiro Compounds ,controlled study ,human ,Furans ,010405 organic chemistry ,Cell growth ,human cell ,Molecular ,HL 60 cell line ,molecular docking ,spiro compound ,In vitro ,thermostability ,0104 chemical sciences ,circular dichroism ,Apoptosis ,G-Quadruplexes ,guanine quadruplex ,030104 developmental biology ,MCF 7 cell line ,Cell culture ,Docking (molecular) ,drug synthesis - Abstract
Numerous complex natural products containing spiroketals framework, with a wide range of important biological activities, have been isolated over the years from marine or terrestrial sources. Many groups investigated the possibility to reduce the complexity of spiroketal natural products while preserving their biological activity, showing that simple natural inspired spiroketals can be privileged scaffolds for new interesting lead compounds. We have synthesized a new structurally simplified spiroketal that has shown a potent antitumor activity against tumor cells of different nature and histotype. The simple spiroketalic structure of this compound has three stereocentres and its synthesis afforded a stereoisomeric mixture. We carried out the synthesis and the characterization of the stereoisomeric mixture, the stereoisomeric separation and the biological evaluation both of the stereoisomeric mixture and the enantiomerically pure spiroketals.
- Published
- 2016
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