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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.

Authors :
Samala G
Devi PB
Nallangi R
Sridevi JP
Saxena S
Yogeeswari P
Sriram D
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.)

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