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Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents

A novel one-pot two step tandem reaction for the synthesis of indolizine-1-carbonitrile derivatives (5a-i) was identified. The route comprises 1,3-dipolar cycloaddition reaction of aromatic aldehyde derivatives (1a-i), malononitrile (2) and 1-(2-(4-bromophenyl)-2-oxoethyl)-2-chloropyridin-1-ium (4)...

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Autores principales: Faghih-Mirzaei, Ehsan, Seifi, Mohammad, Abaszadeh, Mehdi, Zomorodian, Kamiar, Helali, Helia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shaheed Beheshti University of Medical Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094435/
https://www.ncbi.nlm.nih.gov/pubmed/30127812
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author Faghih-Mirzaei, Ehsan
Seifi, Mohammad
Abaszadeh, Mehdi
Zomorodian, Kamiar
Helali, Helia
author_facet Faghih-Mirzaei, Ehsan
Seifi, Mohammad
Abaszadeh, Mehdi
Zomorodian, Kamiar
Helali, Helia
author_sort Faghih-Mirzaei, Ehsan
collection PubMed
description A novel one-pot two step tandem reaction for the synthesis of indolizine-1-carbonitrile derivatives (5a-i) was identified. The route comprises 1,3-dipolar cycloaddition reaction of aromatic aldehyde derivatives (1a-i), malononitrile (2) and 1-(2-(4-bromophenyl)-2-oxoethyl)-2-chloropyridin-1-ium (4) under ultrasound irradiation at room temperature in the presence of triethylamine at acetonitrile. The product compounds were tested against bacteria and fungi. It was revealed that compound 5b had the most antifungal activity (range MICs = 8–32 µg/mL) and compound 5g had the most antibacterial activity (range MICs = 16–256 µg/mL). Molecular docking of compounds (5a-i) into fungal 14α-demethylase and bacterial protein tyrosine phosphatase active sites were also performed and probable binding mode of compounds 5b and 5g were determined.
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spelling pubmed-60944352018-08-20 Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents Faghih-Mirzaei, Ehsan Seifi, Mohammad Abaszadeh, Mehdi Zomorodian, Kamiar Helali, Helia Iran J Pharm Res Original Article A novel one-pot two step tandem reaction for the synthesis of indolizine-1-carbonitrile derivatives (5a-i) was identified. The route comprises 1,3-dipolar cycloaddition reaction of aromatic aldehyde derivatives (1a-i), malononitrile (2) and 1-(2-(4-bromophenyl)-2-oxoethyl)-2-chloropyridin-1-ium (4) under ultrasound irradiation at room temperature in the presence of triethylamine at acetonitrile. The product compounds were tested against bacteria and fungi. It was revealed that compound 5b had the most antifungal activity (range MICs = 8–32 µg/mL) and compound 5g had the most antibacterial activity (range MICs = 16–256 µg/mL). Molecular docking of compounds (5a-i) into fungal 14α-demethylase and bacterial protein tyrosine phosphatase active sites were also performed and probable binding mode of compounds 5b and 5g were determined. Shaheed Beheshti University of Medical Sciences 2018 /pmc/articles/PMC6094435/ /pubmed/30127812 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Faghih-Mirzaei, Ehsan
Seifi, Mohammad
Abaszadeh, Mehdi
Zomorodian, Kamiar
Helali, Helia
Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
title Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
title_full Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
title_fullStr Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
title_full_unstemmed Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
title_short Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents
title_sort design, synthesis, biological evaluation and molecular modeling study of novel indolizine-1-carbonitrile derivatives as potential anti-microbial agents
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094435/
https://www.ncbi.nlm.nih.gov/pubmed/30127812
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