Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of the Brazilian Chemical Society (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532021000501017 |
Resumo: | Seventeen Schiff bases bearing 2-aminothiophene derivatives were designed and synthesized using molecular simplification. The resulting compounds (4a-4q) were evaluated for their in vitro antifungal activity against dermatophytes. Prediction of their druglikeness and pharmacokinetic properties, establishment of their structure-activity relationships (SAR), and cytotoxic evaluation of the most active compounds were performed. Using an eco-friendly procedure, microwave assisted synthesis resulted in compounds in good yields (35-85%). Compounds 4a-4q presented good druglikeness and pharmacokinetic profiles and no cytotoxicity for any cell line tested up to 100 µM. The compounds presenting the best antifungal profiles were 4e, 4f, 4g, 4k, 4l, 4m, 4o and 4p with more than one minimum inhibitory concentration (MIC) value occurring between 16-64 µg mL-1, thus, in some cases better than the reference drug (fluconazole). SAR testing indicated that the presence of halogens and nitro substituents increases antifungal activity. Taken together, the results demonstrate that 2-aminothiophene derivatives are promising lead compounds for the development of antifungal drugs. |
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Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification2-aminothiopheneADMET propertiesantifungal agentsdrug designSchiff baseSeventeen Schiff bases bearing 2-aminothiophene derivatives were designed and synthesized using molecular simplification. The resulting compounds (4a-4q) were evaluated for their in vitro antifungal activity against dermatophytes. Prediction of their druglikeness and pharmacokinetic properties, establishment of their structure-activity relationships (SAR), and cytotoxic evaluation of the most active compounds were performed. Using an eco-friendly procedure, microwave assisted synthesis resulted in compounds in good yields (35-85%). Compounds 4a-4q presented good druglikeness and pharmacokinetic profiles and no cytotoxicity for any cell line tested up to 100 µM. The compounds presenting the best antifungal profiles were 4e, 4f, 4g, 4k, 4l, 4m, 4o and 4p with more than one minimum inhibitory concentration (MIC) value occurring between 16-64 µg mL-1, thus, in some cases better than the reference drug (fluconazole). SAR testing indicated that the presence of halogens and nitro substituents increases antifungal activity. Taken together, the results demonstrate that 2-aminothiophene derivatives are promising lead compounds for the development of antifungal drugs.Sociedade Brasileira de Química2021-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532021000501017Journal of the Brazilian Chemical Society v.32 n.5 2021reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.21577/0103-5053.20210004info:eu-repo/semantics/openAccessLuna,Isadora S.Neves,Wendell W.Lima-Neto,Reginaldo G. deAlbuquerque,Amanda P. B.Pitta,Maíra G. R.Rêgo,Moacyr J. B. M.Neves,Rejane P.Scotti,Marcus T.Mendonça-Junior,Francisco J. B.eng2021-04-28T00:00:00Zoai:scielo:S0103-50532021000501017Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2021-04-28T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
title |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
spellingShingle |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification Luna,Isadora S. 2-aminothiophene ADMET properties antifungal agents drug design Schiff base |
title_short |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
title_full |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
title_fullStr |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
title_full_unstemmed |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
title_sort |
Design, Synthesis and Antifungal Activity of New Schiff Bases Bearing 2-Aminothiophene Derivatives Obtained by Molecular Simplification |
author |
Luna,Isadora S. |
author_facet |
Luna,Isadora S. Neves,Wendell W. Lima-Neto,Reginaldo G. de Albuquerque,Amanda P. B. Pitta,Maíra G. R. Rêgo,Moacyr J. B. M. Neves,Rejane P. Scotti,Marcus T. Mendonça-Junior,Francisco J. B. |
author_role |
author |
author2 |
Neves,Wendell W. Lima-Neto,Reginaldo G. de Albuquerque,Amanda P. B. Pitta,Maíra G. R. Rêgo,Moacyr J. B. M. Neves,Rejane P. Scotti,Marcus T. Mendonça-Junior,Francisco J. B. |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Luna,Isadora S. Neves,Wendell W. Lima-Neto,Reginaldo G. de Albuquerque,Amanda P. B. Pitta,Maíra G. R. Rêgo,Moacyr J. B. M. Neves,Rejane P. Scotti,Marcus T. Mendonça-Junior,Francisco J. B. |
dc.subject.por.fl_str_mv |
2-aminothiophene ADMET properties antifungal agents drug design Schiff base |
topic |
2-aminothiophene ADMET properties antifungal agents drug design Schiff base |
description |
Seventeen Schiff bases bearing 2-aminothiophene derivatives were designed and synthesized using molecular simplification. The resulting compounds (4a-4q) were evaluated for their in vitro antifungal activity against dermatophytes. Prediction of their druglikeness and pharmacokinetic properties, establishment of their structure-activity relationships (SAR), and cytotoxic evaluation of the most active compounds were performed. Using an eco-friendly procedure, microwave assisted synthesis resulted in compounds in good yields (35-85%). Compounds 4a-4q presented good druglikeness and pharmacokinetic profiles and no cytotoxicity for any cell line tested up to 100 µM. The compounds presenting the best antifungal profiles were 4e, 4f, 4g, 4k, 4l, 4m, 4o and 4p with more than one minimum inhibitory concentration (MIC) value occurring between 16-64 µg mL-1, thus, in some cases better than the reference drug (fluconazole). SAR testing indicated that the presence of halogens and nitro substituents increases antifungal activity. Taken together, the results demonstrate that 2-aminothiophene derivatives are promising lead compounds for the development of antifungal drugs. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-05-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532021000501017 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532021000501017 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.21577/0103-5053.20210004 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
Journal of the Brazilian Chemical Society v.32 n.5 2021 reponame:Journal of the Brazilian Chemical Society (Online) instname:Sociedade Brasileira de Química (SBQ) instacron:SBQ |
instname_str |
Sociedade Brasileira de Química (SBQ) |
instacron_str |
SBQ |
institution |
SBQ |
reponame_str |
Journal of the Brazilian Chemical Society (Online) |
collection |
Journal of the Brazilian Chemical Society (Online) |
repository.name.fl_str_mv |
Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ) |
repository.mail.fl_str_mv |
||office@jbcs.sbq.org.br |
_version_ |
1750318184023457792 |