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

Publication date: Available online 10 July 2019Source: Journal of Molecular StructureAuthor(s): Ruchi Verma, Helena I.M. Boshoff, Kriti Arora, Indira Bairy, Mradul Tiwari, G. Varadaraj Bhat, G. Gautham ShenoyAbstractA 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.Graphical abstract
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research

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AbstractA new series of 4-[(substituted benzylidene)-3-[(5-(pyridine-4-yl)-1,3,4-oxadiazole-2-ylthio)-methyl]isoxazol-5(4H)-one (6a –g) and 4-(substituted benzylidene)-3-((benzo[d]thiazol-2-ylthio)methyl)isoxazol-5(4H)-one(8a –g) was synthesized. All the synthesized compounds were screened for antitubercular activity againstMycobacterium tuberculosis H37Ra (ATCC 25177) andMycobacterium bovis BCG (ATCC 35743) and antibacterial activity againstEscherichia coli (NCIM 2576),Pseudomonas flurescence (NCIM 2059),Staphylococcus aureus (NCIM 2602),Bacillus subtilis (NCIM 2162). Amongst the synthesized 1,3,4-oxadiazole a...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research
Publication date: Available online 24 September 2019Source: Journal of Molecular StructureAuthor(s): Romana Machníková, Lucie Janovská, Lucie BrulíkováAbstractHerein, we report the polymer-supported synthesis of new pyrimidine derivatives and their antimycobacterial and antimicrobial activity. Our methodology is based on the fast and efficient solid-phase synthesis having the ability to implement structural diversity from the readily available building blocks through minimum synthetic route and with high yields. Our method was validated in the synthesis of a model chemical library prepare...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
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Source: FEBS Letters - Category: Biochemistry Authors: Tags: Review Source Type: research
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Source: Nuclear Medicine Communications - Category: Nuclear Medicine Tags: ORIGINAL ARTICLES Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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