Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies
| Autor: | Andrea Mattevi, Giovanni Ruoppolo, Oronza A. Botrugno, Ciro Mercurio, Paola Dessanti, Saverio Minucci, Sergio Valente, Giuseppe Ciossani, Biagina Marrocco, Mario Varasi, Antonello Mai, Donatella Labella, Roberto Cirilli, Veronica Rodriguez, Bruna Saponara, Paola Vianello |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
Carbamate animal structures Hydrochloride Stereochemistry medicine.medical_treatment Organic Chemistry Tranylcypromine Diastereomer Biochemistry epigenetics leukemia lysine-specific demethylase stereoisomers tranylcypromine Chiral column chromatography chemistry.chemical_compound Enzyme chemistry Drug Discovery medicine Separation method Selectivity medicine.drug |
| Popis: | The pure four diastereomers (11a-d) of trans-benzyl (1-((4-(2-aminocyclopropyl)phenyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate hydrochloride 11, previously described by us as LSD1 inhibitor, were obtained by enantiospecific synthesis/chiral HPLC separation method. Tested in LSD1 and MAO assays, 11b (S,1S,2R) and 11d (R,1S,2R) were the most potent isomers against LSD1 and were less active against MAO-A and practically inactive against MAO-B. In cells, all the four diastereomers induced Gfi-1b and ITGAM gene expression in NB4 cells, accordingly with their LSD1 inhibition, and 11b and 11d inhibited the colony forming potential in murine promyelocytic blasts. |
| Databáze: | OpenAIRE |
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