Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents

Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxybenzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydra...

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Autores principales: Illicachi, Luis Alberto, Montalvo-Acosta, Joel José, Insuasty, Alberto, Quiroga, Jairo, Abonia, Rodrigo, Sortino, Maximiliano, Zacchino, Susana, Insuasty, Braulio
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: MDPI 2020
Materias:
Antifungal Activity
Cyclocondensation Reaction
Chalcones
N-aryl-2-pyrazolines
Density Functional Theory Calculations
DFT Calculations
Acceso en línea:http://hdl.handle.net/2133/19512
http://hdl.handle.net/2133/19512
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-19512
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Antifungal Activity
Cyclocondensation Reaction
Chalcones
N-aryl-2-pyrazolines
Density Functional Theory Calculations
DFT Calculations
spellingShingle Antifungal Activity
Cyclocondensation Reaction
Chalcones
N-aryl-2-pyrazolines
Density Functional Theory Calculations
DFT Calculations
Illicachi, Luis Alberto
Montalvo-Acosta, Joel José
Insuasty, Alberto
Quiroga, Jairo
Abonia, Rodrigo
Sortino, Maximiliano
Zacchino, Susana
Insuasty, Braulio
Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents
topic_facet Antifungal Activity
Cyclocondensation Reaction
Chalcones
N-aryl-2-pyrazolines
Density Functional Theory Calculations
DFT Calculations
description Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxybenzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2- (dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction was carried out in formic acid. The antifungal activity of both series of compounds against eight fungal species was determined. In general, chalcone derivatives 4 showed better activities than pyrazolines 5 against all tested fungi. None of the compounds 4a–g and 5a–g showed activity against the three Aspergillus spp. In contrast, most of the compounds 4 showed moderate to high activities against three dermatophytes (MICs 31.25–62.5 µg/mL), being 4a followed by 4c the most active structures. Interestingly, 4a and 4c possess fungicidal rather than fungistatic activities, with MFC values between 31.25 and 62.5 µg/mL. The comparison of the percentages of inhibition of C. neoformans by the most active compounds 4, allowed us to know the role played by the different substituents of the chalcones’ A-ring. Also the most anti-cryptococcal compounds 4a–c and 4g, were tested in a second panel of five clinical C. neoformans strains in order to have an overview of their inhibition capacity not only of standardized but also of clinical C. neoformans strains. DFT calculations showed that the electrophilicity is the main electronic property to explain the differences in antifungal activities for the synthesized chalcones and pyrazolines compounds. Furthermore, a quantitative reactivity analysis showed that electron-withdrawing substituted chalcones presented the higher electrophilic character and hence, the greater antifungal activities among compounds of series 4.
format article
artículo
publishedVersion
author Illicachi, Luis Alberto
Montalvo-Acosta, Joel José
Insuasty, Alberto
Quiroga, Jairo
Abonia, Rodrigo
Sortino, Maximiliano
Zacchino, Susana
Insuasty, Braulio
author_facet Illicachi, Luis Alberto
Montalvo-Acosta, Joel José
Insuasty, Alberto
Quiroga, Jairo
Abonia, Rodrigo
Sortino, Maximiliano
Zacchino, Susana
Insuasty, Braulio
author_sort Illicachi, Luis Alberto
title Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents
title_short Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents
title_full Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents
title_fullStr Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents
title_full_unstemmed Synthesis and DFT calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1H-pyrazole-1-carbaldehyde derivatives as antifungal agents
title_sort synthesis and dft calculations of novel vanillin-chalcones and their 3-aryl-5-(4-(2- (dimethylamino)- ethoxy)-3-methoxyphenyl)- 4,5-dihydro-1h-pyrazole-1-carbaldehyde derivatives as antifungal agents
publisher MDPI
publishDate 2020
url http://hdl.handle.net/2133/19512
http://hdl.handle.net/2133/19512
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