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Synthesis of sulfonamide, amide and amine hybrid pharmacophore, an entry of new class of carbonic anhydrase II inhibitors and evaluation of chemo-informatics and binding analysis.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2019 May; Vol. 86, pp. 624-630. Date of Electronic Publication: 2019 Feb 10. - Publication Year :
- 2019
-
Abstract
- Selective inhibition of carbonic anhydrase (CA) enzyme is an active area of research for medicinal chemists. In the current account, a hybrid pharmacophore approach was employed to design sulfonamide, amide and amine containing new series of potent carbonic anhydrase II inhibitors. The aromatic fragment associated with pharmacophore was altered suitably in order to find effective inhibitors of CA-II. All the derivatives 4a-4m showed better inhibition compared to the standard acetazolamide. In particular, compound 4l exhibited significant inhibition with IC <subscript>50</subscript> value of 0.01796 ± 0.00036 µM. The chemo-informatics analysis justified that all the designed compounds possess <10 HBA and <5 HBD. The ligands-protein binding analyses showed that 4l confined in the active binding pocket with three hydrogen bonds observed with His63, Asn66 and Thr197 residues.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Amides chemical synthesis
Amides chemistry
Amines chemical synthesis
Amines chemistry
Carbonic Anhydrase II antagonists & inhibitors
Carbonic Anhydrase II metabolism
Carbonic Anhydrase Inhibitors chemical synthesis
Carbonic Anhydrase Inhibitors chemistry
Dose-Response Relationship, Drug
Humans
Hydrogen Bonding
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Sulfonamides chemical synthesis
Sulfonamides chemistry
Amides pharmacology
Amines pharmacology
Carbonic Anhydrase Inhibitors pharmacology
Cheminformatics
Sulfonamides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 86
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30807935
- Full Text :
- https://doi.org/10.1016/j.bioorg.2019.01.060