S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2003 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFRRJ |
Texto Completo: | https://tede.ufrrj.br/jspui/handle/jspui/4307 |
Resumo: | A series of new compounds, N, N'-bis(dialkylphosphoryl)diamines and S, S'- bis(dialkylphosphoryl)l,3-propanedithiols were prepared by a Todd-Atherton reaction of dialkylphosphites with symmetrical diamines or 1,3-propanedithiols in a biphasic system. They were characterized by IR, 1H-NMR, 13C-NMR, 31p-NMR and mass spectrometry. Compounds with butoxy, isobutoxy and isopropoxy groups on the phosphorus atom showed the lowest LD 50 values when tested against Artemia salina, Musca domestica and Stomoxys calcitrans. All the other compounds which showed high LD 50 values were considered non toxic. The pharmacological and toxicological evaluation of N,N'-bis(diisobutylphosphoril)- 1,3-propylenediamine and S,S'-bis(diisobutylphosforil)-1,3-propanedithio| showed them be inactive against mice in a concentration of 200 mg/Kg The effect on the germination and on the growth of lettuce seeds were observed in an assay with bisphosphoroamidates. The results of a molecular modeling study suggest that the biological activity of the compounds may be related to AChE inhibition. Contrary to classical organophophorus AChE inhibitors, the compounds synthetized in this study do not possess a good leaving group, which suggests that they may act only as reversible inhibitors |
id |
UFRRJ-1_28806c0044f97d554db6e22633bb283a |
---|---|
oai_identifier_str |
oai:localhost:jspui/4307 |
network_acronym_str |
UFRRJ-1 |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UFRRJ |
repository_id_str |
|
spelling |
Costa, Jo?o Batista Neves dahttp://lattes.cnpq.br/8678051184959173Costa, Jo?o Batista Neves daSilva, Jo?o Francisco Caja?ba daMoya Borja, Gonzalo EfrainSant' Anna, Carlos Maur?cio RabelloRumjanek, Victor Marcoshttp://lattes.cnpq.br/9880304801982512Santos, Viviane Martins Rebello dos2020-12-29T15:53:02Z2003-12-05SANTOS, Viviane Martins Rebello dos. S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos. 2003. 304 f. Tese (Doutorado em Qu?mica) - Instituto de Ci?ncias Exatas, Universidade Federal Rural do Rio de Janeiro, Serop?dica-RJ, 2003.https://tede.ufrrj.br/jspui/handle/jspui/4307A series of new compounds, N, N'-bis(dialkylphosphoryl)diamines and S, S'- bis(dialkylphosphoryl)l,3-propanedithiols were prepared by a Todd-Atherton reaction of dialkylphosphites with symmetrical diamines or 1,3-propanedithiols in a biphasic system. They were characterized by IR, 1H-NMR, 13C-NMR, 31p-NMR and mass spectrometry. Compounds with butoxy, isobutoxy and isopropoxy groups on the phosphorus atom showed the lowest LD 50 values when tested against Artemia salina, Musca domestica and Stomoxys calcitrans. All the other compounds which showed high LD 50 values were considered non toxic. The pharmacological and toxicological evaluation of N,N'-bis(diisobutylphosphoril)- 1,3-propylenediamine and S,S'-bis(diisobutylphosforil)-1,3-propanedithio| showed them be inactive against mice in a concentration of 200 mg/Kg The effect on the germination and on the growth of lettuce seeds were observed in an assay with bisphosphoroamidates. The results of a molecular modeling study suggest that the biological activity of the compounds may be related to AChE inhibition. Contrary to classical organophophorus AChE inhibitors, the compounds synthetized in this study do not possess a good leaving group, which suggests that they may act only as reversible inhibitorsUma s?rie de novos N,N'-bis(dialquilfosforil)diaminas e S,S'-bis(dialquilfosforil)-l,3- propanoditiol foram sintetizados pela rea??o de Todd-Atherton modificada, onde fosfitos de dialquila reagem com diaminas sim?tricas ou com 1,3-propanoditiol num sistema bif?sico. Os compostos foram caracterizados por espectrometria de IV, RMN-1H, RMN-13C, RMN-31P e massa. Os compostos com os grupos but?xido, isobut?xido e isoprop?xido, ligados ao ?tomo de f?sforo, apresentam menores valores de DL 50, quando testados contra Artemia salina, Musca domestica e Stomoxys calcitrans. Todos os outros compostos apresentam valores muito maiores e foram considerados n?o t?xicos. Avaliou-se o efeito farmacol?gico e toxicol?gico de N,N'-bis(disobutilfosforil)-l,3-propilenodiamina e S,S'- bis(diisobutilfosforil)-l,3-propanoditiol em camundongos, e estes n?o apresentam atividade t?xica at? a concentra??o de 200 mg/Kg. Os resultados de modelagem molecular sugerem que as atividades biol?gicas dos compostos podem estar relacionadas com a inbi??o da acetilcolinesterase, j? que os inseticidas organofosforados atuam como inibidores cl?ssicos da ACHE. As estruturas sintetizadas neste trabalho n?o apresentam um bom grupo de sa?da ligado ao ?tomo P, sugerindo uma atua??o apenas como inibidores revers?veis da enzima. Foram observados os efeitos de inibi??o da germina??o e do crescimento das sementes de alface (Lactuca sativa) nos ensaios com bisfosforoamidatosSubmitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2020-12-29T15:53:02Z No. of bitstreams: 1 2003 - Viviane Martins Rebello dos Santos.pdf: 7685089 bytes, checksum: 55f422c8505e3fe6bdeda42b4c9ed3f2 (MD5)Made available in DSpace on 2020-12-29T15:53:02Z (GMT). No. of bitstreams: 1 2003 - Viviane Martins Rebello dos Santos.pdf: 7685089 bytes, checksum: 55f422c8505e3fe6bdeda42b4c9ed3f2 (MD5) Previous issue date: 2003-12-05Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPESapplication/pdfhttps://tede.ufrrj.br/retrieve/63681/2003%20-%20Viviane%20Martins%20Rebello%20dos%20Santos.pdf.jpgporUniversidade Federal Rural do Rio de JaneiroPrograma de P?s-Gradua??o em Qu?micaUFRRJBrasilInstituto de Ci?ncias ExatasBisphosphoramidatesBishosphorodithiolatesbiological activityQu?micaS?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFRRJinstname:Universidade Federal Rural do Rio de Janeiro (UFRRJ)instacron:UFRRJTHUMBNAIL2003 - Viviane Martins Rebello dos Santos.pdf.jpg2003 - Viviane Martins Rebello dos Santos.pdf.jpgimage/jpeg3794http://localhost:8080/tede/bitstream/jspui/4307/4/2003+-+Viviane+Martins+Rebello+dos+Santos.pdf.jpgcb3844227c60aea9d8db6f938cf38b3cMD54TEXT2003 - Viviane Martins Rebello dos Santos.pdf.txt2003 - Viviane Martins Rebello dos Santos.pdf.txttext/plain3630http://localhost:8080/tede/bitstream/jspui/4307/3/2003+-+Viviane+Martins+Rebello+dos+Santos.pdf.txt757de7da88cc592ab25428dc479e3caeMD53ORIGINAL2003 - Viviane Martins Rebello dos Santos.pdf2003 - Viviane Martins Rebello dos Santos.pdfapplication/pdf7685089http://localhost:8080/tede/bitstream/jspui/4307/2/2003+-+Viviane+Martins+Rebello+dos+Santos.pdf55f422c8505e3fe6bdeda42b4c9ed3f2MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82089http://localhost:8080/tede/bitstream/jspui/4307/1/license.txt7b5ba3d2445355f386edab96125d42b7MD51jspui/43072021-06-03 20:25:42.257oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttps://tede.ufrrj.br/PUBhttps://tede.ufrrj.br/oai/requestbibliot@ufrrj.br||bibliot@ufrrj.bropendoar:2021-06-03T23:25:42Biblioteca Digital de Teses e Dissertações da UFRRJ - Universidade Federal Rural do Rio de Janeiro (UFRRJ)false |
dc.title.por.fl_str_mv |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
title |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
spellingShingle |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos Santos, Viviane Martins Rebello dos Bisphosphoramidates Bishosphorodithiolates biological activity Qu?mica |
title_short |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
title_full |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
title_fullStr |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
title_full_unstemmed |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
title_sort |
S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos |
author |
Santos, Viviane Martins Rebello dos |
author_facet |
Santos, Viviane Martins Rebello dos |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Costa, Jo?o Batista Neves da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8678051184959173 |
dc.contributor.referee1.fl_str_mv |
Costa, Jo?o Batista Neves da |
dc.contributor.referee2.fl_str_mv |
Silva, Jo?o Francisco Caja?ba da |
dc.contributor.referee3.fl_str_mv |
Moya Borja, Gonzalo Efrain |
dc.contributor.referee4.fl_str_mv |
Sant' Anna, Carlos Maur?cio Rabello |
dc.contributor.referee5.fl_str_mv |
Rumjanek, Victor Marcos |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/9880304801982512 |
dc.contributor.author.fl_str_mv |
Santos, Viviane Martins Rebello dos |
contributor_str_mv |
Costa, Jo?o Batista Neves da Costa, Jo?o Batista Neves da Silva, Jo?o Francisco Caja?ba da Moya Borja, Gonzalo Efrain Sant' Anna, Carlos Maur?cio Rabello Rumjanek, Victor Marcos |
dc.subject.eng.fl_str_mv |
Bisphosphoramidates Bishosphorodithiolates biological activity |
topic |
Bisphosphoramidates Bishosphorodithiolates biological activity Qu?mica |
dc.subject.cnpq.fl_str_mv |
Qu?mica |
description |
A series of new compounds, N, N'-bis(dialkylphosphoryl)diamines and S, S'- bis(dialkylphosphoryl)l,3-propanedithiols were prepared by a Todd-Atherton reaction of dialkylphosphites with symmetrical diamines or 1,3-propanedithiols in a biphasic system. They were characterized by IR, 1H-NMR, 13C-NMR, 31p-NMR and mass spectrometry. Compounds with butoxy, isobutoxy and isopropoxy groups on the phosphorus atom showed the lowest LD 50 values when tested against Artemia salina, Musca domestica and Stomoxys calcitrans. All the other compounds which showed high LD 50 values were considered non toxic. The pharmacological and toxicological evaluation of N,N'-bis(diisobutylphosphoril)- 1,3-propylenediamine and S,S'-bis(diisobutylphosforil)-1,3-propanedithio| showed them be inactive against mice in a concentration of 200 mg/Kg The effect on the germination and on the growth of lettuce seeds were observed in an assay with bisphosphoroamidates. The results of a molecular modeling study suggest that the biological activity of the compounds may be related to AChE inhibition. Contrary to classical organophophorus AChE inhibitors, the compounds synthetized in this study do not possess a good leaving group, which suggests that they may act only as reversible inhibitors |
publishDate |
2003 |
dc.date.issued.fl_str_mv |
2003-12-05 |
dc.date.accessioned.fl_str_mv |
2020-12-29T15:53:02Z |
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.citation.fl_str_mv |
SANTOS, Viviane Martins Rebello dos. S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos. 2003. 304 f. Tese (Doutorado em Qu?mica) - Instituto de Ci?ncias Exatas, Universidade Federal Rural do Rio de Janeiro, Serop?dica-RJ, 2003. |
dc.identifier.uri.fl_str_mv |
https://tede.ufrrj.br/jspui/handle/jspui/4307 |
identifier_str_mv |
SANTOS, Viviane Martins Rebello dos. S?ntese, caracteriza??o, modelagem molecular e estudo da atividade biol?gica de novos bisfosforamidatos e bisfosforoditioatos. 2003. 304 f. Tese (Doutorado em Qu?mica) - Instituto de Ci?ncias Exatas, Universidade Federal Rural do Rio de Janeiro, Serop?dica-RJ, 2003. |
url |
https://tede.ufrrj.br/jspui/handle/jspui/4307 |
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 Rural do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de P?s-Gradua??o em Qu?mica |
dc.publisher.initials.fl_str_mv |
UFRRJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Instituto de Ci?ncias Exatas |
publisher.none.fl_str_mv |
Universidade Federal Rural do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFRRJ instname:Universidade Federal Rural do Rio de Janeiro (UFRRJ) instacron:UFRRJ |
instname_str |
Universidade Federal Rural do Rio de Janeiro (UFRRJ) |
instacron_str |
UFRRJ |
institution |
UFRRJ |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFRRJ |
collection |
Biblioteca Digital de Teses e Dissertações da UFRRJ |
bitstream.url.fl_str_mv |
http://localhost:8080/tede/bitstream/jspui/4307/4/2003+-+Viviane+Martins+Rebello+dos+Santos.pdf.jpg http://localhost:8080/tede/bitstream/jspui/4307/3/2003+-+Viviane+Martins+Rebello+dos+Santos.pdf.txt http://localhost:8080/tede/bitstream/jspui/4307/2/2003+-+Viviane+Martins+Rebello+dos+Santos.pdf http://localhost:8080/tede/bitstream/jspui/4307/1/license.txt |
bitstream.checksum.fl_str_mv |
cb3844227c60aea9d8db6f938cf38b3c 757de7da88cc592ab25428dc479e3cae 55f422c8505e3fe6bdeda42b4c9ed3f2 7b5ba3d2445355f386edab96125d42b7 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFRRJ - Universidade Federal Rural do Rio de Janeiro (UFRRJ) |
repository.mail.fl_str_mv |
bibliot@ufrrj.br||bibliot@ufrrj.br |
_version_ |
1800313519157018624 |