Rational drug design based synthesis of novel arylquinolines as anti-tuberculosis agents

Rational drug design based synthesis of novel arylquinolines as anti-tuberculosis agents

A series of novel arylquinoline derivatives was designed retaining significant pharmacophoric features and three dimensional geometry of bedaquiline. In silico ADME study was performed to assess drug likeness and toxicity profiles of the designed molecules. The compounds were evaluated for activity...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2013-11, Vol.23 (22), p.6097-6105
Hauptverfasser: Jain, Puneet P., Degani, Mariam S., Raju, Archana, Ray, Muktikanta, Rajan, M.G.R.
Format: Artikel
Sprache:eng
Schlagworte:
Adenosine Triphosphatases - chemistry
Adenosine Triphosphatases - metabolism
Animals
Antitubercular Agents - chemical synthesis
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Arylquinoline
ATP synthase
Bedaquiline
Binding Sites
Catalysis
Cercopithecus aethiops
Drug Design
Microbial Sensitivity Tests
Models, Molecular
Mycobacterium tuberculosis
Protein Conformation
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Structure-Activity Relationship
Vero Cells
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Zusammenfassung:A series of novel arylquinoline derivatives was designed retaining significant pharmacophoric features and three dimensional geometry of bedaquiline. In silico ADME study was performed to assess drug likeness and toxicity profiles of the designed molecules. The compounds were evaluated for activity against Mycobacterium tuberculosis H37Rv using Resazurin Microtitre Assay (REMA) plate method and cytotoxicity in VERO C1008 cell line. Several of the synthesized compounds exhibited good antituberculosis activity and selectivity, especially compounds, 12i (MIC: 5.18μM and MIC/CC50: 152.86) and 12l (MIC: 5.59μM and MIC/CC50: 160.57). The study opens up a new platform for the development of arylquinoline based drugs for treating tuberculosis.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.09.027