title: Characterization of the binding properties of SIRT2 inhibitors with a N-(3-phenylpropenoyl)-glycine tryptamide backbone.
abstract: SIRT2 inhibitors with a N-(3-phenylpropenoyl)-glycine tryptamide backbone were studied. This backbone has been developed in our group, and it is derived from a compound originally found by virtual screening. In addition, compounds with a smaller 3-phenylpropenoic acid tryptamide backbone were also included in the study. Binding modes for the new compounds and the previously reported compounds were analyzed with molecular modelling methods. The approach, which included a combination of molecular dynamics, molecular docking and cluster analysis, showed that certain docking poses were favourable despite the conformational variation in the target protein. The N-(3-phenylpropenoyl)-glycine tryptamide backbone is also a good backbone for SIRT2 inhibitors, and the series of compounds includes several potent SIRT2 inhibitors.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. Paivi.Kiviranta@uku.fi
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Kiviranta
authors.forename: Heikki S
authors.initials: HS
authors.lastname: Salo
authors.forename: Jukka
authors.initials: J
authors.lastname: Leppänen
authors.forename: Valtteri M
authors.initials: VM
authors.lastname: Rinne
authors.forename: Sergiy
authors.initials: S
authors.lastname: Kyrylenko
authors.forename: Erkki
authors.initials: E
authors.lastname: Kuusisto
authors.forename: Tiina
authors.initials: T
authors.lastname: Suuronen
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.forename: Erik A A
authors.initials: EA
authors.lastname: Wallén
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016000:Cluster Analysis; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002934:Cinnamates; D004791:Enzyme Inhibitors; D014363:Tryptamines; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins; D005998:Glycine