scholarly journals Aminobenzosuberone Scaffold as a Modular Chemical Tool for the Inhibition of Therapeutically Relevant M1 Aminopeptidases

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2607 ◽  
Author(s):  
Emmanuel Salomon ◽  
Marjorie Schmitt ◽  
Anil Marapaka ◽  
Athanasios Stamogiannos ◽  
Germain Revelant ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Selective Inhibition ◽  
Serine Endopeptidases

The synthesis of racemic substituted 7-amino-5,7,8,9-tetrahydrobenzocyclohepten-6-one hydrochlorides was optimized to enhance reproducibility and increase the overall yield. In order to investigate their specificity, series of enzyme inhibition assays were carried out against a diversity of proteases, covering representative members of aspartic, cysteine, metallo and serine endopeptidases and including eight members of the monometallic M1 family of aminopeptidases as well as two members of the bimetallic M17 and M28 aminopeptidase families. This aminobenzosuberone scaffold indeed demonstrated selective inhibition of M1 aminopeptidases to the exclusion of other tested protease families; it was particularly potent against mammalian APN and its bacterial/parasitic orthologues EcPepN and PfAM1.

scholarly journals Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5358
Author(s):  
Narayan D. Chaurasiya ◽  
Jacob Midiwo ◽  
Pankaj Pandey ◽  
Regina N. Bwire ◽  
Robert J. Doerksen ◽  
...  
Keyword(s):  
Natural Products ◽  
Enzyme Inhibition ◽  
Selective Inhibition ◽  
Monoamine Oxidase A ◽  
Inhibition Kinetics ◽  
Free Energies ◽  
Mao B ◽  
Mao A ◽  
Enzyme Inhibition Kinetics ◽  
Binding Free Energies

A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 1–3 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 4–6) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC50 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders.

Stroma-derived factor 1alpha induces a selective inhibition of human erythroid development via the functional upregulation of Fas/CD95 ligand

2000 ◽  
Vol 111 (2) ◽  
pp. 432-440 ◽  
Author(s):  
Davide Gibellini ◽  
Alessandra Bassini ◽  
Maria Carla Re ◽  
Cristina Ponti ◽  
Sebastiano Miscia ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Cd95 Ligand ◽  
Erythroid Development

Increased response preparation overshadows neurophysiological evidence of proactive selective inhibition.

2018 ◽  
Vol 11 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Neil M. Drummond ◽  
Erin K. Cressman ◽  
Anthony N. Carlsen
Keyword(s):  
Selective Inhibition ◽  
Response Preparation

Selective inhibition of chemokine CCL2/MCP-1 reduces experimental pulmonary hypertension

Pneumologie ◽  
2013 ◽  
Vol 67 (05) ◽  
Author(s):  
D Kosanovic ◽  
BK Dahal ◽  
C Vroom ◽  
E Bieniek ◽  
H Ardeschir Ghofrani ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Selective Inhibition
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