| Autor: |
Ferreira PM; Departamento de Biofísica e Fisiologia, Universidade Federal do Piauí, Teresina, PI, Brasil., Da Costa PM; Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil., Costa Ade M; Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil., Lima DJ; Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil., Drumond RR; Universidade Federal do Piauí, Teresina, PI, Brasil., Silva Jdo N; Universidade Federal do Piauí, Teresina, PI, Brasil., Moreira DR; Departamento de Ciências Farmacêuticas, Universidade Federal do Pernambuco, Recife, PE, Brasil., De Oliveira Filho GB; Departamento de Ciências Farmacêuticas, Universidade Federal do Pernambuco, Recife, PE, Brasil., Ferreira JM; Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, Fortaleza, CE, Brasil., De Queiroz MG; Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, Fortaleza, CE, Brasil., Leite AC; Departamento de Ciências Farmacêuticas, Universidade Federal do Pernambuco, Recife, PE, Brasil., Pessoa C; Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil. |
| Abstrakt: |
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 vivo tumor 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. |
