Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Anais da Academia Brasileira de Ciências (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652021000800704 |
Resumo: | Abstract Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 μg/mL and MFC 62.5 μg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 μg/mL), and C. tropicalis (MIC 31.2 μg/mL and MFC 125 μg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained. |
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Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloidsAntifungal activityCandida albicansmarine sponge alkaloidssynergistic effecttime-kill assay3-Alkylpyridine alkaloid analogsAbstract Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 μg/mL and MFC 62.5 μg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 μg/mL), and C. tropicalis (MIC 31.2 μg/mL and MFC 125 μg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.Academia Brasileira de Ciências2021-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652021000800704Anais da Academia Brasileira de Ciências v.93 suppl.4 2021reponame:Anais da Academia Brasileira de Ciências (Online)instname:Academia Brasileira de Ciências (ABC)instacron:ABC10.1590/0001-3765202120200944info:eu-repo/semantics/openAccessANDRADE,JÉSSICA T.LIMA,WILLIAM G.BARBOSA,CAMILA S.GONÇALVES,ALESSANDRA M.M.N.SILVA,MAYRA K.P.MORAIS,FERNANDA B.PALUMBO,JULIANA M.C.VIANA,GUSTAVO H.R.FERREIRA,JAQUELINE M.S.eng2021-11-19T00:00:00Zoai:scielo:S0001-37652021000800704Revistahttp://www.scielo.br/aabchttps://old.scielo.br/oai/scielo-oai.php||aabc@abc.org.br1678-26900001-3765opendoar:2021-11-19T00:00Anais da Academia Brasileira de Ciências (Online) - Academia Brasileira de Ciências (ABC)false |
dc.title.none.fl_str_mv |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
title |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
spellingShingle |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids ANDRADE,JÉSSICA T. Antifungal activity Candida albicans marine sponge alkaloids synergistic effect time-kill assay 3-Alkylpyridine alkaloid analogs |
title_short |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
title_full |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
title_fullStr |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
title_full_unstemmed |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
title_sort |
Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids |
author |
ANDRADE,JÉSSICA T. |
author_facet |
ANDRADE,JÉSSICA T. LIMA,WILLIAM G. BARBOSA,CAMILA S. GONÇALVES,ALESSANDRA M.M.N. SILVA,MAYRA K.P. MORAIS,FERNANDA B. PALUMBO,JULIANA M.C. VIANA,GUSTAVO H.R. FERREIRA,JAQUELINE M.S. |
author_role |
author |
author2 |
LIMA,WILLIAM G. BARBOSA,CAMILA S. GONÇALVES,ALESSANDRA M.M.N. SILVA,MAYRA K.P. MORAIS,FERNANDA B. PALUMBO,JULIANA M.C. VIANA,GUSTAVO H.R. FERREIRA,JAQUELINE M.S. |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
ANDRADE,JÉSSICA T. LIMA,WILLIAM G. BARBOSA,CAMILA S. GONÇALVES,ALESSANDRA M.M.N. SILVA,MAYRA K.P. MORAIS,FERNANDA B. PALUMBO,JULIANA M.C. VIANA,GUSTAVO H.R. FERREIRA,JAQUELINE M.S. |
dc.subject.por.fl_str_mv |
Antifungal activity Candida albicans marine sponge alkaloids synergistic effect time-kill assay 3-Alkylpyridine alkaloid analogs |
topic |
Antifungal activity Candida albicans marine sponge alkaloids synergistic effect time-kill assay 3-Alkylpyridine alkaloid analogs |
description |
Abstract Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 μg/mL and MFC 62.5 μg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 μg/mL), and C. tropicalis (MIC 31.2 μg/mL and MFC 125 μg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01 |
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=S0001-37652021000800704 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652021000800704 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/0001-3765202120200944 |
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 |
Academia Brasileira de Ciências |
publisher.none.fl_str_mv |
Academia Brasileira de Ciências |
dc.source.none.fl_str_mv |
Anais da Academia Brasileira de Ciências v.93 suppl.4 2021 reponame:Anais da Academia Brasileira de Ciências (Online) instname:Academia Brasileira de Ciências (ABC) instacron:ABC |
instname_str |
Academia Brasileira de Ciências (ABC) |
instacron_str |
ABC |
institution |
ABC |
reponame_str |
Anais da Academia Brasileira de Ciências (Online) |
collection |
Anais da Academia Brasileira de Ciências (Online) |
repository.name.fl_str_mv |
Anais da Academia Brasileira de Ciências (Online) - Academia Brasileira de Ciências (ABC) |
repository.mail.fl_str_mv |
||aabc@abc.org.br |
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1754302871215538176 |