Molecular modeling studies toward the structural optimization of new cyclopeptide-based HDAC inhibitors modeled on the natural product FR235222.
The natural cyclopeptide FR235222 is a potent HDAC inhibitor displaying relevant multiple anticancer effects and is considered an attractive lead compound for the generation of new and more effective antitumor therapeutics. Recently, we have synthesized a small collection of FR235222 simplified analogues which showed interesting biological activities. These results encouraged us to further explore the structural determinants responsible for the activity of this class of HDAC inhibitors in order to gain guidelines for the rational design of new derivatives with putative higher affinity for this target. In the present paper, we report the results obtained, docking these ligands in the binding pocket of HDLP, an HDAC homologue.
Di Micco
Simone
S
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano, Salerno, Italy.
Terracciano
Stefania
S
Bruno
Ines
I
Rodriquez
Manuela
M
Riccio
Raffaele
R
Taddei
Maurizio
M
Bifulco
Giuseppe
G
D000465:Algorithms; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D001688:Biological Products / Q000138:chemical synthesis / Q000494:pharmacology*; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001688:Biological Products; D004791:Enzyme Inhibitors; C474179:FR 235222; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic