6533b7defe1ef96bd1275f24
RESEARCH PRODUCT
Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation.
Valeria La PietraPaola ContiLuciana MarinelliEttore NovellinoLucia TamboriniCarlo De MicheliSilvana GrassoRoberta EttariSanto PrevitiMaria ZappalàIlenia C. AngeloTanja SchirmeisterAndrea Pintosubject
InhibitorMolecular modelCell SurvivalClinical BiochemistryTrypanosoma brucei bruceiAntiprotozoal AgentsPharmaceutical ScienceMolecular modelingCysteine Proteinase InhibitorsBiochemistryCell Linechemistry.chemical_compoundMiceStructure-Activity RelationshipCysteine ProteasesDrug DiscoveryAnimalsMolecular Biology3-Bromo isoxazolinechemistry.chemical_classificationDipeptide-likeDipeptideBinding SitesOrganic ChemistryDipeptidesIsoxazolesCombinatorial chemistryProtein Structure TertiaryMolecular Docking SimulationCysteine EndopeptidasesEnzymeRhodesainchemistryWarheadDocking (molecular)Drug DesignMolecular MedicineRhodesain Dipeptide-like 3-Bromo isoxazoline Inhibitor Molecular modelingdescription
Novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation were developed; some of them possess K(i) values in the micromolar range. We studied the structure-activity relationship of these derivatives and we performed docking studies, which allowed us to find out the key interactions established by the inhibitors with the target enzyme. Biological results indicate that the nature of the P2 and P3 substituents and their binding to the S2/S3 pockets is strictly interdependent.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 | Bioorganicmedicinal chemistry |