Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors
| Autor: | Raffaella Amici, Ciro Mercurio, Andrea Colombo, Maria Carmela Fulco, Luca Sartori, Florian Thaler, Giulio Dondio, Saverio Minucci, Stefania Gagliardi, Roberto Boggio, Loris Moretti, Giacomo Carenzi, Agnese Abate, Mario Varasi |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Models Molecular Molecular model Histone Deacetylases 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Structure–activity relationship Moiety Humans Spiro Compounds ADME Pharmacology Hydroxamic acid biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry General Medicine Histone Deacetylase Inhibitors 030104 developmental biology Histone Biochemistry Chromones biology.protein Histone deacetylase Piperidine |
| Zdroj: | European journal of medicinal chemistry. 108 |
| ISSN: | 1768-3254 |
| Popis: | In the last decades, inhibitors of histone deacetylases (HDAC) have become an important class of anti-cancer agents. In a previous study we described the synthesis of spiro[chromane-2,4'-piperidine]hydroxamic acid derivatives able to inhibit histone deacetylase enzymes. Herein, we present our exploration for new derivatives by replacing the piperidine moiety with various cycloamines. The goal was to obtain highly potent compounds with a good in vitro ADME profile. In addition, molecular modeling studies unravelled the binding mode of these inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect