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Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir

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Resumo:The derivatization of ACV with amino acids has been used for the development of ACV prodrugs. In fact, the valine derivative of ACV – valacyclovir – is a pro-drug of widespread use in herpes treatment. Mitra and co-workers have recently reported the synthesis and properties of novel dipeptide prodrugs of ACV, two of which are included in the present work (3c and 3d) [1,2]. The compounds 3a-f prepared were screened for their in vitro antimicrobial activity against Gram positive (Bacillus cereus, Bacillus subtilis) and Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and also for their fungicidal activity using Candida albicans. The antimicrobial activities were evaluated by diameter measurement of haloes formed by growth inhibition caused by compounds 3 at different concentrations in DMSO [3]. Compounds 3 exhibited antimicrobial activity preferentially against Gram-positive bacteria and were all inactive against Pseudomonas aeruginosa. The minimal inhibitory concentrations (MIC) could be determined for some of the compounds in the concentration range assayed. Further dilutions are being done for MIC determination of most compounds against B. cereus and B. subtilis. The determined MIC were significantly lower than those of typical standards such as ampicilline, cloramphenicol or cyclohexamide. The parent drug, ACV, was also assayed and found to be less active than the corresponding dipeptide ester derivatives. These results suggest that compounds 3 might be activated by bacterial peptidases or actively transported through bacterial cell membrane.
Autores principais:Pereira, Cláudia S.G.P.
Outros Autores:Santos, Cledir; Barreira, João C.M.; Moreira, Rui; Ferreira, Isabel C.F.R.; Estevinho, Leticia M.; Gomes, Paula
Ano:2005
País:Portugal
Tipo de documento:documento de conferência
Tipo de acesso:acesso aberto
Instituição associada:Instituto Politécnico de Bragança
Idioma:inglês
Origem:Biblioteca Digital do IPB
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author Pereira, Cláudia S.G.P.
author2 Santos, Cledir
Barreira, João C.M.
Moreira, Rui
Ferreira, Isabel C.F.R.
Estevinho, Leticia M.
Gomes, Paula
author2_role author
author
author
author
author
author
author_facet Pereira, Cláudia S.G.P.
Santos, Cledir
Barreira, João C.M.
Moreira, Rui
Ferreira, Isabel C.F.R.
Estevinho, Leticia M.
Gomes, Paula
author_role author
contributor_name_str_mv Biblioteca Digital do IPB
country_str PT
creators_json_str [{\"Person.name\":\"Pereira, Cláudia S.G.P.\"},{\"Person.name\":\"Santos, Cledir\"},{\"Person.name\":\"Barreira, João C.M.\",\"Person.identifier.orcid\":\"0000-0003-1233-0990\"},{\"Person.name\":\"Moreira, Rui\"},{\"Person.name\":\"Ferreira, Isabel C.F.R.\",\"Person.identifier.orcid\":\"0000-0003-4910-4882\"},{\"Person.name\":\"Estevinho, Leticia M.\",\"Person.identifier.orcid\":\"0000-0002-9249-1948\"},{\"Person.name\":\"Gomes, Paula\"}]
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datacite.creators.creator.creatorName.fl_str_mv Pereira, Cláudia S.G.P.
Santos, Cledir
Barreira, João C.M.
Moreira, Rui
Ferreira, Isabel C.F.R.
Estevinho, Leticia M.
Gomes, Paula
datacite.date.Accepted.fl_str_mv 2005-01-01T00:00:00Z
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datacite.date.embargoed.fl_str_mv 2011-03-23T11:42:18Z
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datacite.titles.title.fl_str_mv Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
dc.contributor.none.fl_str_mv Biblioteca Digital do IPB
dc.creator.none.fl_str_mv Pereira, Cláudia S.G.P.
Santos, Cledir
Barreira, João C.M.
Moreira, Rui
Ferreira, Isabel C.F.R.
Estevinho, Leticia M.
Gomes, Paula
dc.date.Accepted.fl_str_mv 2005-01-01T00:00:00Z
dc.date.available.fl_str_mv 2011-03-23T11:42:18Z
dc.date.embargoed.fl_str_mv 2011-03-23T11:42:18Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10198/3724
dc.language.none.fl_str_mv eng
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.title.fl_str_mv Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_c94f
description The derivatization of ACV with amino acids has been used for the development of ACV prodrugs. In fact, the valine derivative of ACV – valacyclovir – is a pro-drug of widespread use in herpes treatment. Mitra and co-workers have recently reported the synthesis and properties of novel dipeptide prodrugs of ACV, two of which are included in the present work (3c and 3d) [1,2]. The compounds 3a-f prepared were screened for their in vitro antimicrobial activity against Gram positive (Bacillus cereus, Bacillus subtilis) and Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and also for their fungicidal activity using Candida albicans. The antimicrobial activities were evaluated by diameter measurement of haloes formed by growth inhibition caused by compounds 3 at different concentrations in DMSO [3]. Compounds 3 exhibited antimicrobial activity preferentially against Gram-positive bacteria and were all inactive against Pseudomonas aeruginosa. The minimal inhibitory concentrations (MIC) could be determined for some of the compounds in the concentration range assayed. Further dilutions are being done for MIC determination of most compounds against B. cereus and B. subtilis. The determined MIC were significantly lower than those of typical standards such as ampicilline, cloramphenicol or cyclohexamide. The parent drug, ACV, was also assayed and found to be less active than the corresponding dipeptide ester derivatives. These results suggest that compounds 3 might be activated by bacterial peptidases or actively transported through bacterial cell membrane.
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person_str_mv Pereira, Cláudia S.G.P.
Santos, Cledir
Barreira, João C.M.
Barreira, João C.M.
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0000-0003-1233-0990
Moreira, Rui
Ferreira, Isabel C.F.R.
Ferreira, Isabel C.F.R.
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Estevinho, Leticia M.
Estevinho, Leticia M.
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Gomes, Paula
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spelling engenThe derivatization of ACV with amino acids has been used for the development of ACV prodrugs. In fact, the valine derivative of ACV – valacyclovir – is a pro-drug of widespread use in herpes treatment. Mitra and co-workers have recently reported the synthesis and properties of novel dipeptide prodrugs of ACV, two of which are included in the present work (3c and 3d) [1,2]. The compounds 3a-f prepared were screened for their in vitro antimicrobial activity against Gram positive (Bacillus cereus, Bacillus subtilis) and Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and also for their fungicidal activity using Candida albicans. The antimicrobial activities were evaluated by diameter measurement of haloes formed by growth inhibition caused by compounds 3 at different concentrations in DMSO [3]. Compounds 3 exhibited antimicrobial activity preferentially against Gram-positive bacteria and were all inactive against Pseudomonas aeruginosa. The minimal inhibitory concentrations (MIC) could be determined for some of the compounds in the concentration range assayed. Further dilutions are being done for MIC determination of most compounds against B. cereus and B. subtilis. The determined MIC were significantly lower than those of typical standards such as ampicilline, cloramphenicol or cyclohexamide. The parent drug, ACV, was also assayed and found to be less active than the corresponding dipeptide ester derivatives. These results suggest that compounds 3 might be activated by bacterial peptidases or actively transported through bacterial cell membrane.application/pdfporSynthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovirPereira, Cláudia S.G.P.Santos, CledirPersonalBarreira, João C.M.DSpacehttp://dspace.org/items/4629b12c-39b0-4da8-8b8d-6efba5cf2d81DSpacehttp://dspace.org/items/4629b12c-39b0-4da8-8b8d-6efba5cf2d81BarreiraJoão C.M.ORCIDhttp://orcid.org0000-0003-1233-0990Researcher IDhttps://www.researcherid.comD-8269-2013Scopus Author IDhttps://www.scopus.com54895546900Moreira, RuiPersonalFerreira, Isabel C.F.R.DSpacehttp://dspace.org/items/bd0d1537-2e03-41fb-b27a-140af9c35db8DSpacehttp://dspace.org/items/bd0d1537-2e03-41fb-b27a-140af9c35db8FerreiraIsabel C.F.R.Ciência IDhttps://www.ciencia-id.pt9418-CF95-9919ORCIDhttp://orcid.org0000-0003-4910-4882Researcher IDhttps://www.researcherid.comE-8500-2013Scopus Author IDhttps://www.scopus.com36868826600PersonalEstevinho, Leticia M.DSpacehttp://dspace.org/items/4a1d5ba2-1854-4ca5-89a4-73f35e964df9DSpacehttp://dspace.org/items/4a1d5ba2-1854-4ca5-89a4-73f35e964df9EstevinhoLetícia M.Ciência IDhttps://www.ciencia-id.ptBA14-09D6-A406ORCIDhttp://orcid.org0000-0002-9249-1948Scopus Author IDhttps://www.scopus.com6506577664Scopus Author IDhttps://www.scopus.com57211945650Gomes, PaulaHostingInstitutionOrganizationalBiblioteca Digital do IPBe-mailmailto:dspace@ipb.ptdspace@ipb.ptISSNIsPartOf0036-87092011-03-23T11:42:18Z20052005-01-01T00:00:00ZHandlehttp://hdl.handle.net/10198/3724http://purl.org/coar/access_right/c_abf2open access178606 bytesother research producthttp://purl.org/coar/resource_type/c_c94fconference objecthttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://bibliotecadigital.ipb.pt/bitstreams/04c2a351-1cb9-4d74-b46e-b1c17edf7f61/downloadSupplement 1, Scientia Pharmaceutica, 73 (2) 2005- Abstracts of the Contributions of the Joint Meeting on Medicinal ChemistryViena, Áustria
spellingShingle Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
Pereira, Cláudia S.G.P.
title Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
title_full Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
title_fullStr Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
title_full_unstemmed Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
title_short Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
title_sort Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
url http://hdl.handle.net/10198/3724
visible 1