RESUMO
Ring opening of allobetulone gave either seco-acid 8 or di-acid 4. These acids were converted into esters that were screened by Ellman's assay. A dibutenylester of low cytotoxicity (NIH 3T3 murine embryonic fibroblasts) was shown to be a good mixed-type inhibitor (Ki=3.39, Ki'=2.26µM) for acetylcholinesterase.
Assuntos
Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Animais , Inibidores da Colinesterase/síntese química , Humanos , Cinética , Camundongos , Células NIH 3T3 , Relação Estrutura-Atividade , Triterpenos/síntese químicaRESUMO
A variety of allobetulin derivatives was synthesized from allobetulin or allobetulone. These compounds were screened for their cytotoxic activity using a photometric SRB assay employing six different human tumor cell lines. In summary, opening of ring A of allobetulin in general lowers the cytotoxicity, but the 2,3-seco diethyl ester was highly cytotoxic and remarkable selective for A549 lung carcinoma cells while being significantly less cytotoxic for non-malignant mouse fibroblasts. The introduction of an amino group at position C-3 in the allobetulin skeleton enhances cytotoxicity and furnishes highly cytotoxic compounds. Their selectivity to distinguish between cancer cell and non-malignant cell depends on the configuration at position C-3.
Assuntos
Antineoplásicos/síntese química , Citotoxinas/síntese química , Triterpenos/síntese química , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Triterpenos Pentacíclicos , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia , Ácido BetulínicoRESUMO
Several novel esters and amides of maslinic acid were prepared. Their evaluation for cytotoxic activity with a panel of human cancer cell lines using a sulforhodamine B (SRB) assay revealed for some of them a noteworthy activity. The results from annexinV-FITC and caspase-assays as well as from DNA laddering experiments provided evidence for an apoptotic cell death. A diacetylated benzylamide (15) induced a G1/G0 arrest in tumor cells. It also displayed an extraordinary cytotoxicity against human ovarian cancer cells but a 300 times lower toxicity for non-malignant primary human fibroblasts.