Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents

Ruchi Verma, Helena I.M. Boshoff, Kriti Arora, Indira Bairy, Mradul Tiwari, Bhat G. Varadaraj, G. Gautham Shenoy

Research output: Contribution to journalArticle

Abstract

A new series of novel triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20–40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20–40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein–ligand complex and the protein–ligand interaction in detail.

Original languageEnglish
JournalDrug Development Research
DOIs
Publication statusAccepted/In press - 01-01-2019

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Triclosan
Antitubercular Agents
Molecular Dynamics Simulation
Microbial Sensitivity Tests
Bacillus subtilis
Mycobacterium tuberculosis
Computer Simulation
Staphylococcus aureus
Proteins

All Science Journal Classification (ASJC) codes

  • Drug Discovery

Cite this

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title = "Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents",
abstract = "A new series of novel triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20–40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20–40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein–ligand complex and the protein–ligand interaction in detail.",
author = "Ruchi Verma and Boshoff, {Helena I.M.} and Kriti Arora and Indira Bairy and Mradul Tiwari and Varadaraj, {Bhat G.} and Shenoy, {G. Gautham}",
year = "2019",
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doi = "10.1002/ddr.21623",
language = "English",
journal = "Drug Development Research",
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T1 - Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents

AU - Verma, Ruchi

AU - Boshoff, Helena I.M.

AU - Arora, Kriti

AU - Bairy, Indira

AU - Tiwari, Mradul

AU - Varadaraj, Bhat G.

AU - Shenoy, G. Gautham

PY - 2019/1/1

Y1 - 2019/1/1

N2 - A new series of novel triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20–40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20–40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein–ligand complex and the protein–ligand interaction in detail.

AB - A new series of novel triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20–40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20–40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein–ligand complex and the protein–ligand interaction in detail.

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