TY - JOUR
T1 - Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors
AU - Thaler, Florian
AU - Moretti, Loris
AU - Amici, Raffaella
AU - Abate, Agnese
AU - Colombo, Andrea
AU - Carenzi, Giacomo
AU - Fulco, Maria Carmela
AU - Boggio, Roberto
AU - Dondio, Giulio
AU - Gagliardi, Stefania
AU - Minucci, Saverio
AU - Sartori, Luca
AU - Varasi, Mario
AU - Mercurio, Ciro
PY - 2016/1/27
Y1 - 2016/1/27
N2 - 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.
AB - 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.
KW - Antiproliferation
KW - Epigenetics
KW - Histone deacetylases
KW - Molecular modeling
KW - Privileged structures
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U2 - 10.1016/j.ejmech.2015.11.010
DO - 10.1016/j.ejmech.2015.11.010
M3 - Article
AN - SCOPUS:84948399958
VL - 108
SP - 53
EP - 67
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -