Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives

Detalhes bibliográficos
Autor(a) principal: Santos, Marcelo H. dos
Data de Publicação: 2016
Outros Autores: Rosa, Isael A., Almeida, Letícia de, Alves, Karina F., Marques, Marcos J., Fregnan, Antônio M., Silva, Claudinei A., Giacoppo, Juliana O. S., Carvalho, Diogo T., Ramalho, Teodorico C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: LOCUS Repositório Institucional da UFV
Texto Completo: http://dx.doi.org/10.1007/s00044-016-1729-1
http://www.locus.ufv.br/handle/123456789/21872
Resumo: Eight coumarin derivatives (2–8) were synthesized from 7-hydroxy-4-phenylcoumarin 1 and were evaluated for their in vitro leishmanicidal activity against promastigote and amastigote forms of Leishmania amazonensis, as well their toxicity in murine macrophages. Compounds 4 and 7 showed the most significant results against promastigote forms of L. amazonensis. They were at least three-fold more active than 1 and Compound 4 was as effective as Amphotericin B. Compound 4, a 7-O-prenylated derivative, and 7, a tetra- O -acetyl-β- D -glucopyranosyl derivative, presented IC50 values of 21.35 and 10.03 µM against promastigote and IC50 values of 58.10 and 34.93 µM, respectively against amastigote forms. Furthermore, they do not cause toxicity in mammalian or Leishmania cells in vitro. This study shows that these coumarin derivatives are potential prototypes for the development of novel drugs with leishmanicidal activity.
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spelling Santos, Marcelo H. dosRosa, Isael A.Almeida, Letícia deAlves, Karina F.Marques, Marcos J.Fregnan, Antônio M.Silva, Claudinei A.Giacoppo, Juliana O. S.Carvalho, Diogo T.Ramalho, Teodorico C.2018-09-19T11:33:54Z2018-09-19T11:33:54Z2016-10-2715548120http://dx.doi.org/10.1007/s00044-016-1729-1http://www.locus.ufv.br/handle/123456789/21872Eight coumarin derivatives (2–8) were synthesized from 7-hydroxy-4-phenylcoumarin 1 and were evaluated for their in vitro leishmanicidal activity against promastigote and amastigote forms of Leishmania amazonensis, as well their toxicity in murine macrophages. Compounds 4 and 7 showed the most significant results against promastigote forms of L. amazonensis. They were at least three-fold more active than 1 and Compound 4 was as effective as Amphotericin B. Compound 4, a 7-O-prenylated derivative, and 7, a tetra- O -acetyl-β- D -glucopyranosyl derivative, presented IC50 values of 21.35 and 10.03 µM against promastigote and IC50 values of 58.10 and 34.93 µM, respectively against amastigote forms. Furthermore, they do not cause toxicity in mammalian or Leishmania cells in vitro. This study shows that these coumarin derivatives are potential prototypes for the development of novel drugs with leishmanicidal activity.engMedicinal Chemistry Researchv. 26, n. 1, p. 131– 139, jan. 2017Springer Nature Switzerland AG.info:eu-repo/semantics/openAccessCoumarin derivativesLeishmaniasisLeishmania amazonensisSynthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivativesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALartigo.pdfartigo.pdftexto completoapplication/pdf1040542https://locus.ufv.br//bitstream/123456789/21872/1/artigo.pdf248598cdcec1529d396b23a106f94370MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://locus.ufv.br//bitstream/123456789/21872/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILartigo.pdf.jpgartigo.pdf.jpgIM Thumbnailimage/jpeg6013https://locus.ufv.br//bitstream/123456789/21872/3/artigo.pdf.jpg62576288b6e795ca2eeab06c6cef4de8MD53123456789/218722018-09-19 23:00:37.584oai:locus.ufv.br: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Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452018-09-20T02:00:37LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false
dc.title.en.fl_str_mv Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
title Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
spellingShingle Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
Santos, Marcelo H. dos
Coumarin derivatives
Leishmaniasis
Leishmania amazonensis
title_short Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
title_full Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
title_fullStr Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
title_full_unstemmed Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
title_sort Synthesis and in vitro evaluation of leishmanicidal activity of 7-hydroxy-4-phenylcoumarin derivatives
author Santos, Marcelo H. dos
author_facet Santos, Marcelo H. dos
Rosa, Isael A.
Almeida, Letícia de
Alves, Karina F.
Marques, Marcos J.
Fregnan, Antônio M.
Silva, Claudinei A.
Giacoppo, Juliana O. S.
Carvalho, Diogo T.
Ramalho, Teodorico C.
author_role author
author2 Rosa, Isael A.
Almeida, Letícia de
Alves, Karina F.
Marques, Marcos J.
Fregnan, Antônio M.
Silva, Claudinei A.
Giacoppo, Juliana O. S.
Carvalho, Diogo T.
Ramalho, Teodorico C.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos, Marcelo H. dos
Rosa, Isael A.
Almeida, Letícia de
Alves, Karina F.
Marques, Marcos J.
Fregnan, Antônio M.
Silva, Claudinei A.
Giacoppo, Juliana O. S.
Carvalho, Diogo T.
Ramalho, Teodorico C.
dc.subject.pt-BR.fl_str_mv Coumarin derivatives
Leishmaniasis
Leishmania amazonensis
topic Coumarin derivatives
Leishmaniasis
Leishmania amazonensis
description Eight coumarin derivatives (2–8) were synthesized from 7-hydroxy-4-phenylcoumarin 1 and were evaluated for their in vitro leishmanicidal activity against promastigote and amastigote forms of Leishmania amazonensis, as well their toxicity in murine macrophages. Compounds 4 and 7 showed the most significant results against promastigote forms of L. amazonensis. They were at least three-fold more active than 1 and Compound 4 was as effective as Amphotericin B. Compound 4, a 7-O-prenylated derivative, and 7, a tetra- O -acetyl-β- D -glucopyranosyl derivative, presented IC50 values of 21.35 and 10.03 µM against promastigote and IC50 values of 58.10 and 34.93 µM, respectively against amastigote forms. Furthermore, they do not cause toxicity in mammalian or Leishmania cells in vitro. This study shows that these coumarin derivatives are potential prototypes for the development of novel drugs with leishmanicidal activity.
publishDate 2016
dc.date.issued.fl_str_mv 2016-10-27
dc.date.accessioned.fl_str_mv 2018-09-19T11:33:54Z
dc.date.available.fl_str_mv 2018-09-19T11:33:54Z
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dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1007/s00044-016-1729-1
http://www.locus.ufv.br/handle/123456789/21872
dc.identifier.issn.none.fl_str_mv 15548120
identifier_str_mv 15548120
url http://dx.doi.org/10.1007/s00044-016-1729-1
http://www.locus.ufv.br/handle/123456789/21872
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartofseries.pt-BR.fl_str_mv v. 26, n. 1, p. 131– 139, jan. 2017
dc.rights.driver.fl_str_mv Springer Nature Switzerland AG.
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