Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Anais da Academia Brasileira de Ciências (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652015000100313 |
Resumo: | Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells. |
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Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cellscytotoxicityhistological alterationsmurine cellsphthalimide derivativessarcoma 180Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.Academia Brasileira de Ciências2015-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652015000100313Anais da Academia Brasileira de Ciências v.87 n.1 2015reponame:Anais da Academia Brasileira de Ciências (Online)instname:Academia Brasileira de Ciências (ABC)instacron:ABC10.1590/0001-3765201520130345info:eu-repo/semantics/openAccessFERREIRA,PAULO MICHEL PINHEIROCOSTA,PATRICIA MARÇAL DACOSTA,ARINICE DE MENEZESLIMA,DAISY JEREISSATI BARBOSADRUMOND,RENATA ROSADOSILVA,JURANDY DO NASCIMENTOMOREIRA,DIOGO RODRIGO DE MAGALHÃESOLIVEIRA FILHO,GEVÂNIO BEZERRA DEFERREIRA,JAMILE MAGALHÃESQUEIROZ,MARIA GORETTI RODRIGUES DELEITE,ANA CRISTINA LIMAPESSOA,CLÁUDIAeng2015-11-16T00:00:00Zoai:scielo:S0001-37652015000100313Revistahttp://www.scielo.br/aabchttps://old.scielo.br/oai/scielo-oai.php||aabc@abc.org.br1678-26900001-3765opendoar:2015-11-16T00:00Anais da Academia Brasileira de Ciências (Online) - Academia Brasileira de Ciências (ABC)false |
dc.title.none.fl_str_mv |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
title |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
spellingShingle |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells FERREIRA,PAULO MICHEL PINHEIRO cytotoxicity histological alterations murine cells phthalimide derivatives sarcoma 180 |
title_short |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
title_full |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
title_fullStr |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
title_full_unstemmed |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
title_sort |
Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells |
author |
FERREIRA,PAULO MICHEL PINHEIRO |
author_facet |
FERREIRA,PAULO MICHEL PINHEIRO COSTA,PATRICIA MARÇAL DA COSTA,ARINICE DE MENEZES LIMA,DAISY JEREISSATI BARBOSA DRUMOND,RENATA ROSADO SILVA,JURANDY DO NASCIMENTO MOREIRA,DIOGO RODRIGO DE MAGALHÃES OLIVEIRA FILHO,GEVÂNIO BEZERRA DE FERREIRA,JAMILE MAGALHÃES QUEIROZ,MARIA GORETTI RODRIGUES DE LEITE,ANA CRISTINA LIMA PESSOA,CLÁUDIA |
author_role |
author |
author2 |
COSTA,PATRICIA MARÇAL DA COSTA,ARINICE DE MENEZES LIMA,DAISY JEREISSATI BARBOSA DRUMOND,RENATA ROSADO SILVA,JURANDY DO NASCIMENTO MOREIRA,DIOGO RODRIGO DE MAGALHÃES OLIVEIRA FILHO,GEVÂNIO BEZERRA DE FERREIRA,JAMILE MAGALHÃES QUEIROZ,MARIA GORETTI RODRIGUES DE LEITE,ANA CRISTINA LIMA PESSOA,CLÁUDIA |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
FERREIRA,PAULO MICHEL PINHEIRO COSTA,PATRICIA MARÇAL DA COSTA,ARINICE DE MENEZES LIMA,DAISY JEREISSATI BARBOSA DRUMOND,RENATA ROSADO SILVA,JURANDY DO NASCIMENTO MOREIRA,DIOGO RODRIGO DE MAGALHÃES OLIVEIRA FILHO,GEVÂNIO BEZERRA DE FERREIRA,JAMILE MAGALHÃES QUEIROZ,MARIA GORETTI RODRIGUES DE LEITE,ANA CRISTINA LIMA PESSOA,CLÁUDIA |
dc.subject.por.fl_str_mv |
cytotoxicity histological alterations murine cells phthalimide derivatives sarcoma 180 |
topic |
cytotoxicity histological alterations murine cells phthalimide derivatives sarcoma 180 |
description |
Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-03-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652015000100313 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652015000100313 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/0001-3765201520130345 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Academia Brasileira de Ciências |
publisher.none.fl_str_mv |
Academia Brasileira de Ciências |
dc.source.none.fl_str_mv |
Anais da Academia Brasileira de Ciências v.87 n.1 2015 reponame:Anais da Academia Brasileira de Ciências (Online) instname:Academia Brasileira de Ciências (ABC) instacron:ABC |
instname_str |
Academia Brasileira de Ciências (ABC) |
instacron_str |
ABC |
institution |
ABC |
reponame_str |
Anais da Academia Brasileira de Ciências (Online) |
collection |
Anais da Academia Brasileira de Ciências (Online) |
repository.name.fl_str_mv |
Anais da Academia Brasileira de Ciências (Online) - Academia Brasileira de Ciências (ABC) |
repository.mail.fl_str_mv |
||aabc@abc.org.br |
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1754302861218414592 |