title: Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells.
abstract: 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.
authors: Departamento de Biofísica e Fisiologia, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors: Paulo Michel Pinheiro
authors: PM
authors: Ferreira
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors: Patricia Marçal
authors: PM
authors: Da Costa
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors: Arinice de Menezes
authors: Ade M
authors: Costa
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors: Daisy Jereissati Barbosa
authors: DJ
authors: Lima
authors: Universidade Federal do Piauí, Teresina, PI, Brasil.
authors: Renata Rosado
authors: RR
authors: Drumond
authors: Universidade Federal do Piauí, Teresina, PI, Brasil.
authors: Jurandy do Nascimento
authors: Jdo N
authors: Silva
authors: Departamento de Ciências Farmacêuticas, Universidade Federal do Pernambuco, Recife, PE, Brasil.
authors: Diogo Rodrigo de Magalhães
authors: DR
authors: Moreira
authors: Departamento de Ciências Farmacêuticas, Universidade Federal do Pernambuco, Recife, PE, Brasil.
authors: Gevânio Bezerra
authors: GB
authors: De Oliveira Filho
authors: Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors: Jamile Magalhães
authors: JM
authors: Ferreira
authors: Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors: Maria Goretti Rodrigues
authors: MG
authors: De Queiroz
authors: Departamento de Ciências Farmacêuticas, Universidade Federal do Pernambuco, Recife, PE, Brasil.
authors: Ana Cristina Lima
authors: AC
authors: Leite
authors: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors: Cláudia
authors: C
authors: Pessoa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D051379:Mice; D010797:Phthalimides / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D010797:Phthalimides; C037431:phthalimide