Novel Indole-Based Hydrazones as Potent Inhibitors of the α-class Carbonic Anhydrase from Pathogenic Bacterium Vibrio cholerae

Due to the increasing resistance of currently used antimicrobial drugs, there is an urgent problem for the treatment of cholera disease, selective inhibition of the α-class carbonic anhydrases (CA, EC 4.2.1.1) from the pathogenic bacterium (VcCA) presents an alternative therapeutic target. In this s...

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Published in:International journal of molecular sciences 2020-04, Vol.21 (9), p.3131
Main Authors: Demir-Yazıcı, Kübra, Güzel-Akdemir, Özlen, Angeli, Andrea, Supuran, Claudiu T, Akdemir, Atilla
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Antibiotics
Antimicrobial agents
Bacteria
Binding Sites
Carbonic anhydrase
Carbonic Anhydrase Inhibitors - chemistry
Carbonic Anhydrase Inhibitors - pharmacology
Cholera
Crystal structure
Drug development
Enzyme Activation
Enzymes
Epidemics
Gene expression
Hydrazones
Hydrazones - chemistry
Hydrogen bonds
Indoles
Indoles - chemistry
Inhibitors
Ligands
Molecular Conformation
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular modelling
Molecular Structure
Protein Binding
Selectivity
Simulation
Structure-Activity Relationship
Sulfonamides
Therapeutic applications
Vibrio cholerae
Vibrio cholerae - drug effects
Vibrio cholerae - enzymology
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description Due to the increasing resistance of currently used antimicrobial drugs, there is an urgent problem for the treatment of cholera disease, selective inhibition of the α-class carbonic anhydrases (CA, EC 4.2.1.1) from the pathogenic bacterium (VcCA) presents an alternative therapeutic target. In this study, a series of hydrazone derivatives, carrying the 2-(hydrazinocarbonyl)-3-phenyl-1 -indole-5-sulfonamide scaffold, have been evaluated as inhibitors of the VcCA with molecular modeling studies. The results suggest that these compounds may bind to the active site of VcCA. To verify this, VcCA enzyme inhibition studies were performed and as predicted most of the tested compounds displayed potent inhibitory activities against VcCA with three compounds showing values lower than 30 nM. In addition, all these compounds showed selectivity for VcCA and the off-targets hCA I and II.
doi_str_mv 10.3390/ijms21093131
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subjects Amino Acid Sequence
Amino acids
Antibiotics
Antimicrobial agents
Bacteria
Binding Sites
Carbonic anhydrase
Carbonic Anhydrase Inhibitors - chemistry
Carbonic Anhydrase Inhibitors - pharmacology
Cholera
Crystal structure
Drug development
Enzyme Activation
Enzymes
Epidemics
Gene expression
Hydrazones
Hydrazones - chemistry
Hydrogen bonds
Indoles
Indoles - chemistry
Inhibitors
Ligands
Molecular Conformation
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular modelling
Molecular Structure
Protein Binding
Selectivity
Simulation
Structure-Activity Relationship
Sulfonamides
Therapeutic applications
Vibrio cholerae
Vibrio cholerae - drug effects
Vibrio cholerae - enzymology
title Novel Indole-Based Hydrazones as Potent Inhibitors of the α-class Carbonic Anhydrase from Pathogenic Bacterium Vibrio cholerae
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