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Development of novel tetrahydrothieno[2,3-c]pyridine-3-carboxamide based Mycobacterium tuberculosis pantothenate synthetase inhibitors: molecular hybridization from known antimycobacterial leads.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Mar 15; Vol. 22 (6), pp. 1938-47. Date of Electronic Publication: 2014 Feb 06. - Publication Year :
- 2014
-
Abstract
- Twenty six 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide derivatives were designed by molecular hybridization approach using and synthesized from piperidin-4-one by five step synthesis. Compounds were evaluated for Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibition study, in vitro activities against MTB, cytotoxicity against RAW 264.7 cell line. Among the compounds, 6-(4-nitrophenylsulfonyl)-2-(5-nitrothiophene-2-carboxamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide (11) was found to be the most active compound with IC50 of 5.87 ± 0.12 μM against MTB PS, inhibited MTB with MIC of 9.28 μM and it was non-cytotoxic at 50 μM. The binding affinity of the most potent inhibitor 11 was further confirmed biophysically through differential scanning fluorimetry.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antitubercular Agents chemical synthesis
Antitubercular Agents chemistry
Dose-Response Relationship, Drug
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Molecular Structure
Peptide Synthases metabolism
Structure-Activity Relationship
Sulfonamides chemical synthesis
Sulfonamides chemistry
Thiophenes chemical synthesis
Thiophenes chemistry
Antitubercular Agents pharmacology
Drug Design
Enzyme Inhibitors pharmacology
Mycobacterium tuberculosis drug effects
Mycobacterium tuberculosis enzymology
Peptide Synthases antagonists & inhibitors
Sulfonamides pharmacology
Thiophenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24565972
- Full Text :
- https://doi.org/10.1016/j.bmc.2014.01.030