Synthesis, anti-tuberculosis activity, and 3D-QSAR study of ring-substituted-2/4-quinolinecarbaldehyde derivatives

Nayyar, Amit, Malde, Alpeshkumarb, Coutinhob, Evans and Jain, Rahul (2006) Synthesis, anti-tuberculosis activity, and 3D-QSAR study of ring-substituted-2/4-quinolinecarbaldehyde derivatives. Bioorganic & medicinal chemistry, 14 21: 7302-7310. doi:10.1016/j.bmc.2006.06.049

Author Nayyar, Amit
Malde, Alpeshkumarb
Coutinhob, Evans
Jain, Rahul
Title Synthesis, anti-tuberculosis activity, and 3D-QSAR study of ring-substituted-2/4-quinolinecarbaldehyde derivatives
Journal name Bioorganic & medicinal chemistry   Check publisher's open access policy
ISSN 0968-0896
Publication date 2006-01-01
Year available 2006
Sub-type Article (original research)
DOI 10.1016/j.bmc.2006.06.049
Open Access Status
Volume 14
Issue 21
Start page 7302
End page 7310
Total pages 9
Place of publication United Kingdom
Publisher Pergamon/Elsevier
Language eng
Subject 030401 Biologically Active Molecules
030404 Cheminformatics and Quantitative Structure-Activity Relationships
Abstract We have previously identified ring-substituted quinolines as a new structural class of anti-tuberculosis agents. In our ongoing efforts at structural optimization of this class, four series of ring-substituted-2/4-quinolinecarbaldehyde derivatives were synthesized. All twenty-four compounds were synthesized using short and convenient one to two high yielding steps. The newly synthesized compounds were tested in vitro against drug-sensitive Mycobacterium tuberculosis H37Hv strain. Several derivatives were found to be promising inhibitors of M. tuberculosis. For example, derivatives 4a–c (Series 2), 7a–d (Series 3), and 8a–b (Series 4) displayed >90% inhibition at 6.25 μg/mL in the primary assay. The most active compounds, N-(2-fluorophenyl)-N′-quinolin-2-ylmethylene-hydrazine (4a), N-(2-adamantan-1-yl-quinolin-4-ylmethylene)-N′-(4-fluorophenyl)hydrazine (7c), and N-(2-cyclohexyl-quinolin-4-ylmethylene)-N′-(2-fluorophenyl)hydrazine (8a), exhibited 99% inhibition at the lowest tested concentration of 3.125 μg/mL against drug-sensitive M. tuberculosis H37Rv strain. The similarity index based on steric and electrostatic features of the molecules was used, in conjunction with principal component analysis and linear discriminant analysis, successively to classify the molecules based on their activity into two classes. This classification method gives us confidence in predicting the activity class of any new unsynthesized molecule belonging to these series.
Keyword Biochemistry & Molecular Biology
Chemistry, Medicinal
Chemistry, Organic
Biochemistry & Molecular Biology
Pharmacology & Pharmacy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 48 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 02 Feb 2009, 21:22:05 EST by Ms Lynette Adams on behalf of Institute for Molecular Bioscience