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Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons

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Resumo:The synthesis of 20 arylidenecamphors and 15 pyrimidines with camphane skeleton is described in the current report. A modified method for preparation of sterically hindered 2-aminopyrimidines in two steps was demonstrated. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed different MIC values (up to 0.91 μM for ketone 39). Compound 35 demonstrated moderate (8.23 μM), but sustainable activity toward a collection of drug-resistant M. tuberculosis strains. Many of the compounds (especially among 2-aminopyridines 42–56) exhibited good to excellent activity against different strains of pathogenic bacteria and fungi (MIC up to 0.60 μM for compound 50), compared with reference antibiotics. Many of the newly designed compounds possess also in vitro cytotoxicity.
Autores principais:Slavchev, Ivaylo M.
Outros Autores:Mitrev, Yavor; Shivachev, Boris; Valcheva, Violeta; Dogonadze, Marine; Solovieva, Natalia; Vyazovaya, Anna; Mokrousov, Igor; Link, Wolfgang; Jiménez, Lucía; Cautain, Bastien; Mackenzie, Thomas A.; Portugal, Isabel; Lopes, Francisca; Capela, Rita; Perdigão, João; Dobrikov, Georgi M.
Assunto:antibiotics camphor cytotoxicity drug-discovery heterocycles tuberculosi
Ano:2022
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
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author Slavchev, Ivaylo M.
author2 Mitrev, Yavor
Shivachev, Boris
Valcheva, Violeta
Dogonadze, Marine
Solovieva, Natalia
Vyazovaya, Anna
Mokrousov, Igor
Link, Wolfgang
Jiménez, Lucía
Cautain, Bastien
Mackenzie, Thomas A.
Portugal, Isabel
Lopes, Francisca
Capela, Rita
Perdigão, João
Dobrikov, Georgi M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Slavchev, Ivaylo M.
Mitrev, Yavor
Shivachev, Boris
Valcheva, Violeta
Dogonadze, Marine
Solovieva, Natalia
Vyazovaya, Anna
Mokrousov, Igor
Link, Wolfgang
Jiménez, Lucía
Cautain, Bastien
Mackenzie, Thomas A.
Portugal, Isabel
Lopes, Francisca
Capela, Rita
Perdigão, João
Dobrikov, Georgi M.
author_role author
contributor_name_str_mv Repositório Científico de Acesso Aberto da ULisboa
country_str PT
creators_json_txt [{\"Person.name\":\"Slavchev, Ivaylo M.\"},{\"Person.name\":\"Mitrev, Yavor\"},{\"Person.name\":\"Shivachev, Boris\"},{\"Person.name\":\"Valcheva, Violeta\"},{\"Person.name\":\"Dogonadze, Marine\"},{\"Person.name\":\"Solovieva, Natalia\"},{\"Person.name\":\"Vyazovaya, Anna\"},{\"Person.name\":\"Mokrousov, Igor\"},{\"Person.name\":\"Link, Wolfgang\"},{\"Person.name\":\"Jiménez, Lucía\"},{\"Person.name\":\"Cautain, Bastien\"},{\"Person.name\":\"Mackenzie, Thomas A.\"},{\"Person.name\":\"Portugal, Isabel\",\"Person.identifier.orcid\":\"0000-0002-7843-0006\"},{\"Person.name\":\"Lopes, Francisca\",\"Person.identifier.orcid\":\"0000-0002-5350-147X\"},{\"Person.name\":\"Capela, Rita\",\"Person.identifier.orcid\":\"0000-0001-9637-3714\"},{\"Person.name\":\"Perdigão, João\",\"Person.identifier.orcid\":\"0000-0002-0339-1305\"},{\"Person.name\":\"Dobrikov, Georgi M.\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
datacite.creators.creator.creatorName.fl_str_mv Slavchev, Ivaylo M.
Mitrev, Yavor
Shivachev, Boris
Valcheva, Violeta
Dogonadze, Marine
Solovieva, Natalia
Vyazovaya, Anna
Mokrousov, Igor
Link, Wolfgang
Jiménez, Lucía
Cautain, Bastien
Mackenzie, Thomas A.
Portugal, Isabel
Lopes, Francisca
Capela, Rita
Perdigão, João
Dobrikov, Georgi M.
datacite.date.Accepted.fl_str_mv 2022-05-03T00:00:00Z
datacite.date.available.fl_str_mv 2023-08-18T11:27:17Z
datacite.date.embargoed.fl_str_mv 2023-08-18T11:27:17Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_16ec
datacite.subjects.subject.fl_str_mv antibiotics
camphor
cytotoxicity
drug-discovery
heterocycles
tuberculosi
datacite.titles.title.fl_str_mv Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
dc.contributor.none.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
dc.creator.none.fl_str_mv Slavchev, Ivaylo M.
Mitrev, Yavor
Shivachev, Boris
Valcheva, Violeta
Dogonadze, Marine
Solovieva, Natalia
Vyazovaya, Anna
Mokrousov, Igor
Link, Wolfgang
Jiménez, Lucía
Cautain, Bastien
Mackenzie, Thomas A.
Portugal, Isabel
Lopes, Francisca
Capela, Rita
Perdigão, João
Dobrikov, Georgi M.
dc.date.Accepted.fl_str_mv 2022-05-03T00:00:00Z
dc.date.available.fl_str_mv 2023-08-18T11:27:17Z
dc.date.embargoed.fl_str_mv 2023-08-18T11:27:17Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10451/58922
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Wiley-VCH
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_16ec
dc.subject.none.fl_str_mv antibiotics
camphor
cytotoxicity
drug-discovery
heterocycles
tuberculosi
dc.title.fl_str_mv Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description The synthesis of 20 arylidenecamphors and 15 pyrimidines with camphane skeleton is described in the current report. A modified method for preparation of sterically hindered 2-aminopyrimidines in two steps was demonstrated. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed different MIC values (up to 0.91 μM for ketone 39). Compound 35 demonstrated moderate (8.23 μM), but sustainable activity toward a collection of drug-resistant M. tuberculosis strains. Many of the compounds (especially among 2-aminopyridines 42–56) exhibited good to excellent activity against different strains of pathogenic bacteria and fungi (MIC up to 0.60 μM for compound 50), compared with reference antibiotics. Many of the newly designed compounds possess also in vitro cytotoxicity.
dirty 0
eu_rights_str_mv restrictedAccess
format article
fulltext.url.fl_str_mv https://repositorio.ulisboa.pt/bitstreams/77716740-37be-4151-948b-ccdc6cdb714e/download
id ul_64bb22a1ea136e6f0e8f620eef0dc277
identifier.url.fl_str_mv http://hdl.handle.net/10451/58922
instacron_str ul
institution Universidade de Lisboa
instname_str Universidade de Lisboa
language eng
network_acronym_str ul
network_name_str Repositório da Universidade de Lisboa
oai_identifier_str oai:repositorio.ulisboa.pt:10451/58922
organization_str_mv urn:organizationAcronym:ul
person_str_mv Slavchev, Ivaylo M.
Mitrev, Yavor
Shivachev, Boris
Valcheva, Violeta
Dogonadze, Marine
Solovieva, Natalia
Vyazovaya, Anna
Mokrousov, Igor
Link, Wolfgang
Jiménez, Lucía
Cautain, Bastien
Mackenzie, Thomas A.
Portugal, Isabel
Portugal, Isabel
https://www.ciencia-id.pt/E310-5746-C205
E310-5746-C205
http://orcid.org/0000-0002-7843-0006
0000-0002-7843-0006
Lopes, Francisca
Lopes, Francisca
https://www.ciencia-id.pt/3911-17F9-540E
3911-17F9-540E
http://orcid.org/0000-0002-5350-147X
0000-0002-5350-147X
Capela, Rita
Capela, Rita
https://www.ciencia-id.pt/801D-647D-1F16
801D-647D-1F16
http://orcid.org/0000-0001-9637-3714
0000-0001-9637-3714
Perdigão, João
Perdigão, João
https://www.ciencia-id.pt/991C-F26A-9843
991C-F26A-9843
http://orcid.org/0000-0002-0339-1305
0000-0002-0339-1305
Dobrikov, Georgi M.
publishDate 2022
publisher.none.fl_str_mv Wiley-VCH
reponame_str Repositório da Universidade de Lisboa
repository_id_str urn:repositoryAcronym:ul
service_str_mv urn:repositoryAcronym:ul
spelling engWiley-VCHpt_PTThe synthesis of 20 arylidenecamphors and 15 pyrimidines with camphane skeleton is described in the current report. A modified method for preparation of sterically hindered 2-aminopyrimidines in two steps was demonstrated. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed different MIC values (up to 0.91 μM for ketone 39). Compound 35 demonstrated moderate (8.23 μM), but sustainable activity toward a collection of drug-resistant M. tuberculosis strains. Many of the compounds (especially among 2-aminopyridines 42–56) exhibited good to excellent activity against different strains of pathogenic bacteria and fungi (MIC up to 0.60 μM for compound 50), compared with reference antibiotics. Many of the newly designed compounds possess also in vitro cytotoxicity.application/pdfpt_PTSynthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane SkeletonsSlavchev, Ivaylo M.Mitrev, YavorShivachev, BorisValcheva, VioletaDogonadze, MarineSolovieva, NataliaVyazovaya, AnnaMokrousov, IgorLink, WolfgangJiménez, LucíaCautain, BastienMackenzie, Thomas A.PersonalPortugal, IsabelDSpacehttp://dspace.org/items/4484da69-843c-4a20-af02-b3c111f84324DSpacehttp://dspace.org/items/4484da69-843c-4a20-af02-b3c111f84324PortugalIsabelCiência IDhttps://www.ciencia-id.ptE310-5746-C205ORCIDhttp://orcid.org0000-0002-7843-0006PersonalLopes, FranciscaDSpacehttp://dspace.org/items/914c2246-322f-4b77-85e8-d1e0c22e21d6DSpacehttp://dspace.org/items/914c2246-322f-4b77-85e8-d1e0c22e21d6LopesFranciscaCiência IDhttps://www.ciencia-id.pt3911-17F9-540EORCIDhttp://orcid.org0000-0002-5350-147XPersonalCapela, RitaDSpacehttp://dspace.org/items/5a363f6b-fddd-4922-9b78-b145a1d04903DSpacehttp://dspace.org/items/5a363f6b-fddd-4922-9b78-b145a1d04903CapelaRitaCiência IDhttps://www.ciencia-id.pt801D-647D-1F16ORCIDhttp://orcid.org0000-0001-9637-3714Researcher IDhttps://www.researcherid.comA-6002-2016Scopus Author IDhttps://www.scopus.com6602816287PersonalPerdigão, JoãoDSpacehttp://dspace.org/items/26de40fc-fc1d-4ff9-a242-3bb398e3ac1eDSpacehttp://dspace.org/items/26de40fc-fc1d-4ff9-a242-3bb398e3ac1eLucas Mota PerdigãoJoão RubenCiência IDhttps://www.ciencia-id.pt991C-F26A-9843ORCIDhttp://orcid.org0000-0002-0339-1305Scopus Author IDhttps://www.scopus.com24723211800Dobrikov, Georgi M.HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf2365-6549DOIIsPartOf10.1002/slct.2022013392023-08-18T11:27:17Z2022-05-032023-01-04T15:28:02Z2022-05-03T00:00:00ZHandlehttp://hdl.handle.net/10451/58922http://purl.org/coar/access_right/c_16ecrestricted accessantibioticscamphorcytotoxicitydrug-discoveryheterocyclestuberculosi1767273 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/77716740-37be-4151-948b-ccdc6cdb714e/downloadChemistrySelect717e202201339
spellingShingle Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
Slavchev, Ivaylo M.
antibiotics
camphor
cytotoxicity
drug-discovery
heterocycles
tuberculosi
status SINGLETON
subject.fl_str_mv antibiotics
camphor
cytotoxicity
drug-discovery
heterocycles
tuberculosi
title Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
title_full Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
title_fullStr Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
title_full_unstemmed Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
title_short Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
title_sort Synthesis, Characterization and Complex Evaluation of Antibacterial Activity and Cytotoxicity of New Arylmethylidene Ketones and Pyrimidines with Camphane Skeletons
topic antibiotics
camphor
cytotoxicity
drug-discovery
heterocycles
tuberculosi
topic_facet antibiotics
camphor
cytotoxicity
drug-discovery
heterocycles
tuberculosi
url http://hdl.handle.net/10451/58922
visible 1