Synthesis, antitubercular evaluation, molecular docking and molecular dynamics studies of 4,6-disubstituted-2-oxo-dihydropyridine-3-carbonitriles

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

Research output: Contribution to journalArticle

Abstract

A new series of novel diphenyl ether based 2-oxo-dihydropyridine derivatives were synthesized and screened for their in vitro antimycobacterial and antibacterial activities. Most of the synthesized compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain in comparison to triclosan. Among them, compounds 3k and 3q were found to be most active against Mycobacterium tuberculosis H37Rv strain with MIC of 31 and 32 μM respectively. All the compounds were found to be more active against Bacillus subtilis and Staphylococcus aureus than against Pseudomonas aeruginosa and Escherichia coli. Several compounds were found to safe against Vero and HepG2 cell lines. Molecular docking study was utilized to explore the binding mode of the synthesized compounds to the target enzyme InhA. The results showed reasonable binding interactions of synthesized molecules and good dock score. Molecular dynamics studies were performed in order to support the docking results. The compound 3k-InhA complex was found to be more stable and exhibited more interaction when compared to Triclosan. The compounds followed Lipinski rule of five and displayed acceptable pharmacokinetic properties depicted via in silico studies.

Original languageEnglish
Pages (from-to)117-133
Number of pages17
JournalJournal of Molecular Structure
Volume1197
DOIs
Publication statusPublished - 05-12-2019

Fingerprint

Triclosan
Molecular dynamics
Docks
Pharmacokinetics
Bacilli
Escherichia coli
Cells
Derivatives
Molecules
Enzymes
1,4-dihydropyridine
phenyl ether

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

@article{c9ae071ffd8145119a679356c3511e22,
title = "Synthesis, antitubercular evaluation, molecular docking and molecular dynamics studies of 4,6-disubstituted-2-oxo-dihydropyridine-3-carbonitriles",
abstract = "A new series of novel diphenyl ether based 2-oxo-dihydropyridine derivatives were synthesized and screened for their in vitro antimycobacterial and antibacterial activities. Most of the synthesized compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain in comparison to triclosan. Among them, compounds 3k and 3q were found to be most active against Mycobacterium tuberculosis H37Rv strain with MIC of 31 and 32 μM respectively. All the compounds were found to be more active against Bacillus subtilis and Staphylococcus aureus than against Pseudomonas aeruginosa and Escherichia coli. Several compounds were found to safe against Vero and HepG2 cell lines. Molecular docking study was utilized to explore the binding mode of the synthesized compounds to the target enzyme InhA. The results showed reasonable binding interactions of synthesized molecules and good dock score. Molecular dynamics studies were performed in order to support the docking results. The compound 3k-InhA complex was found to be more stable and exhibited more interaction when compared to Triclosan. The compounds followed Lipinski rule of five and displayed acceptable pharmacokinetic properties depicted via in silico studies.",
author = "Ruchi Verma and Boshoff, {Helena I.M.} and Kriti Arora and Indira Bairy and Mradul Tiwari and Bhat, {Varadaraj G.} and Shenoy, {Gautham G.}",
year = "2019",
month = "12",
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doi = "10.1016/j.molstruc.2019.07.035",
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T1 - Synthesis, antitubercular evaluation, molecular docking and molecular dynamics studies of 4,6-disubstituted-2-oxo-dihydropyridine-3-carbonitriles

AU - Verma, Ruchi

AU - Boshoff, Helena I.M.

AU - Arora, Kriti

AU - Bairy, Indira

AU - Tiwari, Mradul

AU - Bhat, Varadaraj G.

AU - Shenoy, Gautham G.

PY - 2019/12/5

Y1 - 2019/12/5

N2 - A new series of novel diphenyl ether based 2-oxo-dihydropyridine derivatives were synthesized and screened for their in vitro antimycobacterial and antibacterial activities. Most of the synthesized compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain in comparison to triclosan. Among them, compounds 3k and 3q were found to be most active against Mycobacterium tuberculosis H37Rv strain with MIC of 31 and 32 μM respectively. All the compounds were found to be more active against Bacillus subtilis and Staphylococcus aureus than against Pseudomonas aeruginosa and Escherichia coli. Several compounds were found to safe against Vero and HepG2 cell lines. Molecular docking study was utilized to explore the binding mode of the synthesized compounds to the target enzyme InhA. The results showed reasonable binding interactions of synthesized molecules and good dock score. Molecular dynamics studies were performed in order to support the docking results. The compound 3k-InhA complex was found to be more stable and exhibited more interaction when compared to Triclosan. The compounds followed Lipinski rule of five and displayed acceptable pharmacokinetic properties depicted via in silico studies.

AB - A new series of novel diphenyl ether based 2-oxo-dihydropyridine derivatives were synthesized and screened for their in vitro antimycobacterial and antibacterial activities. Most of the synthesized compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain in comparison to triclosan. Among them, compounds 3k and 3q were found to be most active against Mycobacterium tuberculosis H37Rv strain with MIC of 31 and 32 μM respectively. All the compounds were found to be more active against Bacillus subtilis and Staphylococcus aureus than against Pseudomonas aeruginosa and Escherichia coli. Several compounds were found to safe against Vero and HepG2 cell lines. Molecular docking study was utilized to explore the binding mode of the synthesized compounds to the target enzyme InhA. The results showed reasonable binding interactions of synthesized molecules and good dock score. Molecular dynamics studies were performed in order to support the docking results. The compound 3k-InhA complex was found to be more stable and exhibited more interaction when compared to Triclosan. The compounds followed Lipinski rule of five and displayed acceptable pharmacokinetic properties depicted via in silico studies.

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