Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://hdl.handle.net/1843/SFSA-9RXETA |
Resumo: | In this work, thirty eight compounds were synthesized from condensation between hydroxybenzaldehydes (ortho, meta, and para) with phenylenediamines (ortho, meta, and para), of aromatic dialdehydes (ortho, meta, and para) with aminophenols (ortho, meta, and para) and benzoic aminoacids (ortho, meta, and para). All the compounds were obtained with yields 53% to 99%. Some of these reactions afforded cyclic compounds, such as benzoimidazole (two compounds) and imineisoindoline (five compounds). Seventeen acyclic bis-imines were reduced to bis-amines using sodium borohydride and cerium chloride. Two palladium complexes were prepared with bis-imines and one bis-amine was converted in to the respective platinum complex. Fifteen new compounds were synthesized in this work. Seventeen synthesized compounds were assayed in vitro against nine humans tumor cell lines: NCI-ADR/RES (ovarian cancer resistant to multiple drugs); NCI-H460 (Lung); PC-3 (prostate); OVCAR-3 (ovary); U251 (gliome, SNC); UACC-62 (melanoma); MCF-7 (breast); HT-29 (colon); K562 (leukemia). The cell line UACC-62 (melanoma) was the most susceptible for the evaluated compounds. Several compounds showed a broad spectrum of action in concentrations from 1 to 10 g/mL. One acyclic bis-imine presented a total inhibition of growth (TIG) four times higher than the positive control (doxorubicin), against the cell line NCI-ADR/RES (resistant ovary). All the compounds, except for the metallic complexes, were evaluated against the following pathogenic fungi of clinical interest: Candida albicans ATCC 18804, Candida krusei ATCC 20298, Candida parapsilosis ATCC 20019, Candida tropicalis ATCC 00750, Candida glabrata ATCC 32608, Cryptococcus neoformans ATCC 32608, Cryptococcus gattii ATCC 28957, and Candida dubliniensis CBS 7987. Several compounds have displayed some kind of activit Cryptococcus neoformans being the most susceptible to the four assayed compounds, showing inhibition levels near thoses achieved with the positive control (fluconazole). The free radical scavenging activity was evaluated for thirty five compounds using DPPH and superoxide anion radical methods. In both procedures the most of the compounds showed better anti-oxidant activities than that achieved with the positive control (resveratrol). In general, the bis-amines were more efficient than bis-imines. |
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Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantesBis-iminasBis-aminasAntitumoralAntioxidanteAntifúngicaAtividade antifúngicaQuímica orgânicaIminasAgentes antineoplásicosAntioxidantesIn this work, thirty eight compounds were synthesized from condensation between hydroxybenzaldehydes (ortho, meta, and para) with phenylenediamines (ortho, meta, and para), of aromatic dialdehydes (ortho, meta, and para) with aminophenols (ortho, meta, and para) and benzoic aminoacids (ortho, meta, and para). All the compounds were obtained with yields 53% to 99%. Some of these reactions afforded cyclic compounds, such as benzoimidazole (two compounds) and imineisoindoline (five compounds). Seventeen acyclic bis-imines were reduced to bis-amines using sodium borohydride and cerium chloride. Two palladium complexes were prepared with bis-imines and one bis-amine was converted in to the respective platinum complex. Fifteen new compounds were synthesized in this work. Seventeen synthesized compounds were assayed in vitro against nine humans tumor cell lines: NCI-ADR/RES (ovarian cancer resistant to multiple drugs); NCI-H460 (Lung); PC-3 (prostate); OVCAR-3 (ovary); U251 (gliome, SNC); UACC-62 (melanoma); MCF-7 (breast); HT-29 (colon); K562 (leukemia). The cell line UACC-62 (melanoma) was the most susceptible for the evaluated compounds. Several compounds showed a broad spectrum of action in concentrations from 1 to 10 g/mL. One acyclic bis-imine presented a total inhibition of growth (TIG) four times higher than the positive control (doxorubicin), against the cell line NCI-ADR/RES (resistant ovary). All the compounds, except for the metallic complexes, were evaluated against the following pathogenic fungi of clinical interest: Candida albicans ATCC 18804, Candida krusei ATCC 20298, Candida parapsilosis ATCC 20019, Candida tropicalis ATCC 00750, Candida glabrata ATCC 32608, Cryptococcus neoformans ATCC 32608, Cryptococcus gattii ATCC 28957, and Candida dubliniensis CBS 7987. Several compounds have displayed some kind of activit Cryptococcus neoformans being the most susceptible to the four assayed compounds, showing inhibition levels near thoses achieved with the positive control (fluconazole). The free radical scavenging activity was evaluated for thirty five compounds using DPPH and superoxide anion radical methods. In both procedures the most of the compounds showed better anti-oxidant activities than that achieved with the positive control (resveratrol). In general, the bis-amines were more efficient than bis-imines.Neste trabalho foram sintetizados trinta e oito compostos a partir da condensacao de hidroxibenzaldeidos (orto, meta e para) com fenilenodiaminas (orto, meta e para), dialdeidos aromaticos (orto, meta e para) com aminofenois (orto, meta e para) e com os acidos aminobenzoicos (orto, meta e para). Todos foram obtidos com rendimentos entre 53% a 99%. Algumas dessas condensacoes resultaram em produtos de ciclizacao, sendo dois derivados de benzoimidazol e cinco derivados de iminoisoindolinas. A partir das dezessete bis-iminas aciclicas, que nao sofreram ciclizacao, onze foram transformadas nos respectivos analogos hidrogenados, mediante reducao com boroidreto de sodio e cloreto de cerio. Duas bis-iminas aciclicas foram transformadas em complexos de paladio e uma bis-amina foi complexada a com platina. Dentre todos os compostos sintetizados, quinze foram ineditos. Dezessete compostos foram avaliados in vitro contra nove linhagens de celulas tumorais humanas: ADR/RES (ovario resistente a multiplos farmacos); U251 (glioma, SNC); MCF-7 (mama); NCI-H460 (pulmao); PC-3 (prostata); OVCAR-3 (ovario); HT-29 (colon); K562 (leucemia); UACC-62 (melanoma), sendo esta ultima a mais susceptivel aos compostos testados. Varios compostos apresentaram um amplo espectro de acao, atuando em concentracoes entre 1 e 10 ¿Ýg/mL. Uma das bis-iminas aciclicas apresentou um valor de inibicao total do crescimento (ITC) quatro vezes maior ao apresentado pelo controle positivo (doxorrubicina), para a linhagem de celula NCI-ADR/RES (ovario resistente). Todos os compostos, exceto os complexos metalicos, foram avaliados contra os seguintes fungos patogenicos de interesse clinico: Candida albicans (ATCC 18804), Candida krusei (ATCC 20298), Candida parapsilosis (ATCC 20019), Candida tropicalis (ATCC 00750), Candida glabrata (ATCC 32608), Cryptococcus neoformans (ATCC 32608), Cryptococcus gattii (ATCC 28957) e Candida dubliniensis (CBS 7987). Varios compostos apresentaram algum tipo de atividade, sendo que a especie Cryptococcus neoformans foi sensivel a quatro dos compostos testados, apresentando valores de inibicao proximos ao controle positivo (fluconazol). A atividade sequestradora de radicais livres foi avaliada para 35 compostos, utilizando os metodos de DPPH e anion superoxido. Esses ensaios revelaram para varios compostos, atividades antioxidantes muito superiores ao controle positivo (resveratrol), sendo as bis-aminas mais eficientes do que as bis-iminas. Universidade Federal de Minas GeraisUFMGDorila Pilo VelosoAdao Aparecido SabinoFernando César de Macedo JúniorMayura Marques M. RubingerRosemeire Brondi AlvesAntonio Flavio de Carvalho AlcantaraLucas Micqueias Arantes2019-08-10T10:21:47Z2019-08-10T10:21:47Z2014-11-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/SFSA-9RXETAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2019-11-14T06:12:03Zoai:repositorio.ufmg.br:1843/SFSA-9RXETARepositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2019-11-14T06:12:03Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.none.fl_str_mv |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
title |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
spellingShingle |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes Lucas Micqueias Arantes Bis-iminas Bis-aminas Antitumoral Antioxidante Antifúngica Atividade antifúngica Química orgânica Iminas Agentes antineoplásicos Antioxidantes |
title_short |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
title_full |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
title_fullStr |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
title_full_unstemmed |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
title_sort |
Síntese de bis-iminas e bis-aminas funcionalizadas e avaliação de suas atividades contra células de câncer, fungos e como antioxidantes |
author |
Lucas Micqueias Arantes |
author_facet |
Lucas Micqueias Arantes |
author_role |
author |
dc.contributor.none.fl_str_mv |
Dorila Pilo Veloso Adao Aparecido Sabino Fernando César de Macedo Júnior Mayura Marques M. Rubinger Rosemeire Brondi Alves Antonio Flavio de Carvalho Alcantara |
dc.contributor.author.fl_str_mv |
Lucas Micqueias Arantes |
dc.subject.por.fl_str_mv |
Bis-iminas Bis-aminas Antitumoral Antioxidante Antifúngica Atividade antifúngica Química orgânica Iminas Agentes antineoplásicos Antioxidantes |
topic |
Bis-iminas Bis-aminas Antitumoral Antioxidante Antifúngica Atividade antifúngica Química orgânica Iminas Agentes antineoplásicos Antioxidantes |
description |
In this work, thirty eight compounds were synthesized from condensation between hydroxybenzaldehydes (ortho, meta, and para) with phenylenediamines (ortho, meta, and para), of aromatic dialdehydes (ortho, meta, and para) with aminophenols (ortho, meta, and para) and benzoic aminoacids (ortho, meta, and para). All the compounds were obtained with yields 53% to 99%. Some of these reactions afforded cyclic compounds, such as benzoimidazole (two compounds) and imineisoindoline (five compounds). Seventeen acyclic bis-imines were reduced to bis-amines using sodium borohydride and cerium chloride. Two palladium complexes were prepared with bis-imines and one bis-amine was converted in to the respective platinum complex. Fifteen new compounds were synthesized in this work. Seventeen synthesized compounds were assayed in vitro against nine humans tumor cell lines: NCI-ADR/RES (ovarian cancer resistant to multiple drugs); NCI-H460 (Lung); PC-3 (prostate); OVCAR-3 (ovary); U251 (gliome, SNC); UACC-62 (melanoma); MCF-7 (breast); HT-29 (colon); K562 (leukemia). The cell line UACC-62 (melanoma) was the most susceptible for the evaluated compounds. Several compounds showed a broad spectrum of action in concentrations from 1 to 10 g/mL. One acyclic bis-imine presented a total inhibition of growth (TIG) four times higher than the positive control (doxorubicin), against the cell line NCI-ADR/RES (resistant ovary). All the compounds, except for the metallic complexes, were evaluated against the following pathogenic fungi of clinical interest: Candida albicans ATCC 18804, Candida krusei ATCC 20298, Candida parapsilosis ATCC 20019, Candida tropicalis ATCC 00750, Candida glabrata ATCC 32608, Cryptococcus neoformans ATCC 32608, Cryptococcus gattii ATCC 28957, and Candida dubliniensis CBS 7987. Several compounds have displayed some kind of activit Cryptococcus neoformans being the most susceptible to the four assayed compounds, showing inhibition levels near thoses achieved with the positive control (fluconazole). The free radical scavenging activity was evaluated for thirty five compounds using DPPH and superoxide anion radical methods. In both procedures the most of the compounds showed better anti-oxidant activities than that achieved with the positive control (resveratrol). In general, the bis-amines were more efficient than bis-imines. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-11-07 2019-08-10T10:21:47Z 2019-08-10T10:21:47Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/SFSA-9RXETA |
url |
http://hdl.handle.net/1843/SFSA-9RXETA |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais UFMG |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais UFMG |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
instname_str |
Universidade Federal de Minas Gerais (UFMG) |
instacron_str |
UFMG |
institution |
UFMG |
reponame_str |
Repositório Institucional da UFMG |
collection |
Repositório Institucional da UFMG |
repository.name.fl_str_mv |
Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
repository.mail.fl_str_mv |
repositorio@ufmg.br |
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1816829893030182912 |