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Benzo[d]thiazol-2-yl(piperazin-1-yl)methanones as new anti-mycobacterial chemotypes: Design, synthesis, biological evaluation and 3D-QSAR studies.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2016 Jun 30; Vol. 116, pp. 187-199. Date of Electronic Publication: 2016 Mar 23. - Publication Year :
- 2016
-
Abstract
- The benzo[d]thiazol-2-yl(piperazin-1-yl)methanones scaffold has been identified as new anti-mycobacterial chemotypes. Thirty-six structurally diverse benzo[d]thiazole-2-carboxamides have been prepared and subjected to assessment of their potential anti-tubercular activity through in vitro testing against Mycobacterium tuberculosis H37Rv strain and evaluation of cytotoxicity against RAW 264.7 cell lines. Seventeen compounds showed anti-mycobacterial potential having MICs in the low (1-10) μM range. The 5-trifluoromethyl benzo[d]thiazol-2-yl(piperazin-1-yl)methanones emerged to be the most promising resulting in six positive hits (2.35-7.94 μM) and showed low-cytotoxicity (<50% inhibition at 50 μg/mL). The therapeutic index of these hits is 8-64. The quantitative structure activity relationship has been established adopting a statistically reliable CoMFA model showing high prediction (rpred(2)=0.718,rncv(2)=0.995).<br /> (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Animals
Antitubercular Agents chemistry
Antitubercular Agents toxicity
Chemistry Techniques, Synthetic
Mice
Microbial Sensitivity Tests
Models, Molecular
Molecular Conformation
Mycobacterium tuberculosis drug effects
Piperazine
Piperazines chemistry
Piperazines toxicity
RAW 264.7 Cells
Antitubercular Agents chemical synthesis
Antitubercular Agents pharmacology
Drug Design
Piperazines chemical synthesis
Piperazines pharmacology
Quantitative Structure-Activity Relationship
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 116
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27061982
- Full Text :
- https://doi.org/10.1016/j.ejmech.2016.03.060