Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina

Detalhes bibliográficos
Autor(a) principal: Amim, Raquel dos Santos
Data de Publicação: 2017
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/15652
Resumo: In the present work we describe the synthesis of thiosemicarbazones (TSCs) derived from pyrazinamide, its metal complexes of Ga3+, Bi3+ and Sb3+ as well as p-nitrophenylethylenediamine-derived Schiff bases. These compounds have been developed in order to investigate their potential as prototypes of antituberculosis and/or antitumor drugs. In this context, 2-pyrazineformamide thiosemicarbazone (HPzAm4DH, 1) and its derivatives substituted at N4 by methyl (HPzAm4M, 2), ethyl (HPzAm4E, 3), cyclohexyl (HPzAm4Cex, 4) and phenyl (HPzAm4Ph, 5) were prepared, whose data of melting point, IR and NMR spectroscopies and electrospray ionization mass spectrometry (ESI-MS) confirmed its purity and yield. Novel complexes were obtained with the thiosemicarbazones and the metal ions of interest. The Ga3+ complexes (610) have been prepared from TSC and gallium nitrate in the 2:1 ratio and exhibit the general formula [Ga(L)2]NO3, where L is the anionic thiosemicarbazone. Bi3+(1115) and Sb3+ (1620) complexes have been prepared from TSC and metal choride (1:1 ratio) and showed the general formula [M(L)Cl2] (where M = Bi3+ou Sb3+). All complexes were characterized, when possible, by melting point, conductivimetry, IR, electronic and NMR spectroscopies as well as ESI-MS. The biological action of all compounds has been investigated. The TSC haven t exhibit action against the tumor cell lines HCT116 (colon adenocarcinoma), OVCAR8 (ovarian cancer) and SF295 (glioblastoma multiforme) at 5g/mL and against Mycobacterium tuberculosis strain, the main bacterial species causing tuberculosis, in the concentration maximum of 100 g/mL. Ga3+ complexes (710) don t demonstrate significant cytotoxic effects against the tumor cell lines, except compound (9), which is more cytotoxic to MCF7, PC3 and HCT116 cells when compared to the reference drugs cisplatin and etoposide. In general, the activity of these complexes against M. tuberculosis bacteria is better than the free thiosemicarbazones, confirming that Ga3+ coordination resulted in compounds more potent against this bacterium. Bi3+ complexes (1115) have not shown significant activity against the tumor cells tested as well as against M. tuberculosis. The investigated Sb3+ complexes (1620) also have not shown activity against the tumor cells under study. Nonetheless, coordination to Sb3+ led to a significant increase in activity against M. tuberculosis, especially for complexes 17, 18 and 19, which show a minimum inhibitory concentration of 25 μg/mL. Twelve molecules containing the p-nitrobenzene group (2132) have also been synthesized and characterized by IR and NMR spectroscopies as well as ESI-MS. Among the compounds, 21, 29, 30 and 32 inhibit the growth of HCT116 cells by more than 90%. All compounds were inactive against M. tuberculosis at the concentrations tested, with the exception of 24 and 29
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spelling Lessa, Josane Alveshttp://lattes.cnpq.br/8402296847454322Carvalho, Nakédia Maysa Freitashttp://lattes.cnpq.br/0775160605053287Marques, Lippy Fariahttp://lattes.cnpq.br/6940752683134954Lanznaster, Mauriciohttp://lattes.cnpq.br/5123336948991939Casellato, Annelisehttp://lattes.cnpq.br/6666301937868490http://lattes.cnpq.br/6203552502796372Amim, Raquel dos Santos2021-01-07T18:58:50Z2018-07-202017-01-23AMIM, Raquel dos Santos. Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina. 2017. 202 f. Tese (Doutorado em Química ambiental; Polímeros) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2017.http://www.bdtd.uerj.br/handle/1/15652In the present work we describe the synthesis of thiosemicarbazones (TSCs) derived from pyrazinamide, its metal complexes of Ga3+, Bi3+ and Sb3+ as well as p-nitrophenylethylenediamine-derived Schiff bases. These compounds have been developed in order to investigate their potential as prototypes of antituberculosis and/or antitumor drugs. In this context, 2-pyrazineformamide thiosemicarbazone (HPzAm4DH, 1) and its derivatives substituted at N4 by methyl (HPzAm4M, 2), ethyl (HPzAm4E, 3), cyclohexyl (HPzAm4Cex, 4) and phenyl (HPzAm4Ph, 5) were prepared, whose data of melting point, IR and NMR spectroscopies and electrospray ionization mass spectrometry (ESI-MS) confirmed its purity and yield. Novel complexes were obtained with the thiosemicarbazones and the metal ions of interest. The Ga3+ complexes (610) have been prepared from TSC and gallium nitrate in the 2:1 ratio and exhibit the general formula [Ga(L)2]NO3, where L is the anionic thiosemicarbazone. Bi3+(1115) and Sb3+ (1620) complexes have been prepared from TSC and metal choride (1:1 ratio) and showed the general formula [M(L)Cl2] (where M = Bi3+ou Sb3+). All complexes were characterized, when possible, by melting point, conductivimetry, IR, electronic and NMR spectroscopies as well as ESI-MS. The biological action of all compounds has been investigated. The TSC haven t exhibit action against the tumor cell lines HCT116 (colon adenocarcinoma), OVCAR8 (ovarian cancer) and SF295 (glioblastoma multiforme) at 5g/mL and against Mycobacterium tuberculosis strain, the main bacterial species causing tuberculosis, in the concentration maximum of 100 g/mL. Ga3+ complexes (710) don t demonstrate significant cytotoxic effects against the tumor cell lines, except compound (9), which is more cytotoxic to MCF7, PC3 and HCT116 cells when compared to the reference drugs cisplatin and etoposide. In general, the activity of these complexes against M. tuberculosis bacteria is better than the free thiosemicarbazones, confirming that Ga3+ coordination resulted in compounds more potent against this bacterium. Bi3+ complexes (1115) have not shown significant activity against the tumor cells tested as well as against M. tuberculosis. The investigated Sb3+ complexes (1620) also have not shown activity against the tumor cells under study. Nonetheless, coordination to Sb3+ led to a significant increase in activity against M. tuberculosis, especially for complexes 17, 18 and 19, which show a minimum inhibitory concentration of 25 μg/mL. Twelve molecules containing the p-nitrobenzene group (2132) have also been synthesized and characterized by IR and NMR spectroscopies as well as ESI-MS. Among the compounds, 21, 29, 30 and 32 inhibit the growth of HCT116 cells by more than 90%. All compounds were inactive against M. tuberculosis at the concentrations tested, with the exception of 24 and 29No presente trabalho é descrita a síntese de tiossemicarbazonas (TSCs) derivadas de pirazinamida, seus complexos metálicos de Ga3+, Bi3+ e Sb3+e de bases de Schiff derivadas de p-nitrofeniletilenodiamina. Esses compostos foram desenvolvidos com o objetivo de investigar seu potencial como protótipos de fármacos antituberculose e/ou antitumoral. Nesse contexto, foram preparados 2-pirazinoformamida tiossemicarbazona (HPzAm4DH, 1) e seus derivados substituídos em N4 por metil (HPzAm4M, 2), etil (HPzAm4E, 3), cicloexil (HPzAm4Cex, 4), fenil(HPzAm4Ph, 5), cujos dados de pontos de fusão, espectroscopias no IV e de RMN e espectrometria de massas com ionização por electrospray(ESI-MS) confirmaram sua pureza e obtenção. A partir das tiossemicarbazonas foram obtidos novos complexos com os íons metálicos de interesse. Os complexos de Ga3+ (610) foram obtidos à partir da proporção TSC:nitrato de gálio(III) (2:1) e apresentam estrutura geral [Ga(L)2]NO3, onde L- corresponde à TSC desprotonada. Os complexos de Bi3+ (1115) e os de Sb3+ (1620) foram obtidos à partir de TSC e cloreto metálico na proporção 1:1 e apresentam estrutura geral [M(L)Cl2] (onde M = Bi3+ou Sb3+). Os complexos metálicos foram caracterizados, quando possível, por ponto de fusão, condutivimetria, espectroscopias no IV, eletrônica e de RMN e espectrometria de massas. Foi investigada a ação biológica de todos os compostos. Das tiossemicarbazonas sintetizadas, nenhuma teve atividade significativa contra as células tumorais HCT116 (adenocarcinoma de colon), OVCAR8 (câncer de ovário) e SF295 (glioblastoma multiforme) a 5g/mL e contra cepas de Mycobacterium tuberculosis, a principal espécie de bactéria causadora de tuberculose, na concentração máxima de 100 g/mL. Complexos de Ga3+ (7-10) não demonstraram efeitos citotóxicos significativos contra as linhagens de células tumorais, com exceção do composto (9), o qual foi mais citotóxico às linhagens MCF7, PC3 e HCT116 quando comparados com os fármacos de referência cisplatina e etoposídeo. Em geral, a atividade desses complexos contra bactéria M. tuberculosis é melhor que a das tiossemicarbazonas não coordenadas, confirmando que a coordenação ao Ga3+ resultou em compostos mais potentes contra essa bactéria. Os complexos de Bi3+ (1115) não apresentaram atividade significativa contra as células tumorais testadas como também contra M. tuberculosis. Os complexos de Sb3+ investigados (1620) não apresentaram atividade contra as células tumorais em estudo. No entanto, a coordenação a Sb3+ levou ao aumento significativo de atividade contra M. tuberculosis, sobretudo para os complexos 17, 18 e 19, os quais apresentaram concentração inibitória mínima de 25g/mL. Foram sintetizadas ainda 12 moléculas contendo o grupo p-nitrobenzeno (2132), que foram caracterizadas por espectroscopia no infravermelho, RMN e ESI-MS. Dentre os compostos, destacaram-se 21, 29, 30 e 32 que inibiram em mais de 90% o crescimento de células HCT116. Todos os compostos mostraram-se inativos contra M. tuberculosis nas concentrações testadas, com exceção de 24 e 29Submitted by Boris Flegr (boris@uerj.br) on 2021-01-07T18:58:50Z No. of bitstreams: 1 Raquel dos Santos Amim.pdf: 9907549 bytes, checksum: a8c6eb9ba71a448bfbdc13d9b68df4ac (MD5)Made available in DSpace on 2021-01-07T18:58:50Z (GMT). No. of bitstreams: 1 Raquel dos Santos Amim.pdf: 9907549 bytes, checksum: a8c6eb9ba71a448bfbdc13d9b68df4ac (MD5) Previous issue date: 2017-01-23Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em QuímicaUERJBRCentro de Tecnologia e Ciências::Instituto de QuímicaThiosemicarbazonepyrazinamidemetal complexSchiff basiscytotoxic activitytuberculosisTiossemicarbazonapirazinamidacomplexo metálicobases de Schiffatividade citotóxicatuberculoseCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICASíntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiaminaSynthesis, characterization, and cytotoxic and antituberculosis potential of thiosemicarbazones, their gallium(III), bismuth(III), antimony(III) complexes and Schiff bases derived from p-nitrophenylethylenediamineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALRaquel dos Santos Amim.pdfapplication/pdf9907549http://www.bdtd.uerj.br/bitstream/1/15652/1/Raquel+dos+Santos+Amim.pdfa8c6eb9ba71a448bfbdc13d9b68df4acMD511/156522024-02-27 14:47:37.604oai:www.bdtd.uerj.br:1/15652Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-27T17:47:37Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
dc.title.alternative.eng.fl_str_mv Synthesis, characterization, and cytotoxic and antituberculosis potential of thiosemicarbazones, their gallium(III), bismuth(III), antimony(III) complexes and Schiff bases derived from p-nitrophenylethylenediamine
title Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
spellingShingle Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
Amim, Raquel dos Santos
Thiosemicarbazone
pyrazinamide
metal complex
Schiff basis
cytotoxic activity
tuberculosis
Tiossemicarbazona
pirazinamida
complexo metálico
bases de Schiff
atividade citotóxica
tuberculose
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA
title_short Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
title_full Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
title_fullStr Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
title_full_unstemmed Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
title_sort Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina
author Amim, Raquel dos Santos
author_facet Amim, Raquel dos Santos
author_role author
dc.contributor.advisor1.fl_str_mv Lessa, Josane Alves
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8402296847454322
dc.contributor.referee1.fl_str_mv Carvalho, Nakédia Maysa Freitas
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0775160605053287
dc.contributor.referee2.fl_str_mv Marques, Lippy Faria
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/6940752683134954
dc.contributor.referee3.fl_str_mv Lanznaster, Mauricio
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/5123336948991939
dc.contributor.referee4.fl_str_mv Casellato, Annelise
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6666301937868490
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6203552502796372
dc.contributor.author.fl_str_mv Amim, Raquel dos Santos
contributor_str_mv Lessa, Josane Alves
Carvalho, Nakédia Maysa Freitas
Marques, Lippy Faria
Lanznaster, Mauricio
Casellato, Annelise
dc.subject.eng.fl_str_mv Thiosemicarbazone
pyrazinamide
metal complex
Schiff basis
cytotoxic activity
tuberculosis
topic Thiosemicarbazone
pyrazinamide
metal complex
Schiff basis
cytotoxic activity
tuberculosis
Tiossemicarbazona
pirazinamida
complexo metálico
bases de Schiff
atividade citotóxica
tuberculose
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA
dc.subject.por.fl_str_mv Tiossemicarbazona
pirazinamida
complexo metálico
bases de Schiff
atividade citotóxica
tuberculose
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA
description In the present work we describe the synthesis of thiosemicarbazones (TSCs) derived from pyrazinamide, its metal complexes of Ga3+, Bi3+ and Sb3+ as well as p-nitrophenylethylenediamine-derived Schiff bases. These compounds have been developed in order to investigate their potential as prototypes of antituberculosis and/or antitumor drugs. In this context, 2-pyrazineformamide thiosemicarbazone (HPzAm4DH, 1) and its derivatives substituted at N4 by methyl (HPzAm4M, 2), ethyl (HPzAm4E, 3), cyclohexyl (HPzAm4Cex, 4) and phenyl (HPzAm4Ph, 5) were prepared, whose data of melting point, IR and NMR spectroscopies and electrospray ionization mass spectrometry (ESI-MS) confirmed its purity and yield. Novel complexes were obtained with the thiosemicarbazones and the metal ions of interest. The Ga3+ complexes (610) have been prepared from TSC and gallium nitrate in the 2:1 ratio and exhibit the general formula [Ga(L)2]NO3, where L is the anionic thiosemicarbazone. Bi3+(1115) and Sb3+ (1620) complexes have been prepared from TSC and metal choride (1:1 ratio) and showed the general formula [M(L)Cl2] (where M = Bi3+ou Sb3+). All complexes were characterized, when possible, by melting point, conductivimetry, IR, electronic and NMR spectroscopies as well as ESI-MS. The biological action of all compounds has been investigated. The TSC haven t exhibit action against the tumor cell lines HCT116 (colon adenocarcinoma), OVCAR8 (ovarian cancer) and SF295 (glioblastoma multiforme) at 5g/mL and against Mycobacterium tuberculosis strain, the main bacterial species causing tuberculosis, in the concentration maximum of 100 g/mL. Ga3+ complexes (710) don t demonstrate significant cytotoxic effects against the tumor cell lines, except compound (9), which is more cytotoxic to MCF7, PC3 and HCT116 cells when compared to the reference drugs cisplatin and etoposide. In general, the activity of these complexes against M. tuberculosis bacteria is better than the free thiosemicarbazones, confirming that Ga3+ coordination resulted in compounds more potent against this bacterium. Bi3+ complexes (1115) have not shown significant activity against the tumor cells tested as well as against M. tuberculosis. The investigated Sb3+ complexes (1620) also have not shown activity against the tumor cells under study. Nonetheless, coordination to Sb3+ led to a significant increase in activity against M. tuberculosis, especially for complexes 17, 18 and 19, which show a minimum inhibitory concentration of 25 μg/mL. Twelve molecules containing the p-nitrobenzene group (2132) have also been synthesized and characterized by IR and NMR spectroscopies as well as ESI-MS. Among the compounds, 21, 29, 30 and 32 inhibit the growth of HCT116 cells by more than 90%. All compounds were inactive against M. tuberculosis at the concentrations tested, with the exception of 24 and 29
publishDate 2017
dc.date.issued.fl_str_mv 2017-01-23
dc.date.available.fl_str_mv 2018-07-20
dc.date.accessioned.fl_str_mv 2021-01-07T18:58:50Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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status_str publishedVersion
dc.identifier.citation.fl_str_mv AMIM, Raquel dos Santos. Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina. 2017. 202 f. Tese (Doutorado em Química ambiental; Polímeros) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2017.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/15652
identifier_str_mv AMIM, Raquel dos Santos. Síntese, caracterização e potencial citotóxico e antituberculose de tiossemicarbazonas, seus complexos de gálio(III), bismuto(III), antimônio(III) e de bases de Schiff derivadas de p-nitrofeniletilenodiamina. 2017. 202 f. Tese (Doutorado em Química ambiental; Polímeros) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2017.
url http://www.bdtd.uerj.br/handle/1/15652
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dc.publisher.initials.fl_str_mv UERJ
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Centro de Tecnologia e Ciências::Instituto de Química
publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
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