RESUMO
The synthesis of a newangular analog 11 of cyclozonarone was achieved via Diels-Alder reaction between a sesquiterpene-1,3-diene and 1,4-benzoquinone. The cytotoxic activity of ent-cyclozonarone [(+)-10] and the angular (-)-cyclozonarone analog 11 has been determined in three human cancer cell lines and in normal fibroblasts using the sulforhodamine B assay. The analyzed isomers induce cell death in different cancer cell lines by eliciting nuclear condensation and fragmentation, decreasing mitochondrial membrane permeability and increasing caspase-3 activity, all traits indicating apoptosis, with the effects of (+)-10 being stronger than those of 11 in all cases.
Assuntos
Apoptose/efeitos dos fármacos , Núcleo Celular/metabolismo , Citotoxinas , Fibroblastos/metabolismo , Sesquiterpenos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/patologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Fibroblastos/patologia , Humanos , Sesquiterpenos/síntese química , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Two new compounds 2ß-acetoxy-15-phenyl-(22,25-acetoxy)-ent-labda-8(17), 13(E)-diene (9) and 2ß-hydroxy-15-phenyl-(22,24,26-trimethoxy)-ent-labda-8(17),13(E)-diene (10) have been prepared by an Electrophilic Aromatic Substitution (EAS) reaction between diterpenyl allylic alcohols and 1,4-hydroquinone or 1,3,5-trimethoxybenzene using BF(3).Et(2)O as a catalyst. These compounds, along with a series of natural ent-labdanes 3-8, have been evaluated for their in vitro cytotoxic activities against cultured human cancer cells of PC-3 and DU-145 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma and dermal human fibroblasts (DHF). Some compounds displayed inhibition at µM IC(50 )values.
Assuntos
Antineoplásicos/síntese química , Diterpenos/química , Hidroquinonas/síntese química , Hidroquinonas/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Masculino , Neoplasias da Próstata/tratamento farmacológicoRESUMO
The synthesis and structural determination of two new diterpenylhydroquinones: 2beta-acetoxy-15-phenyl-(22,25-dihydroxy)-ent-labda-8(17),13(E)-diene(1) and 2beta-hydroxy-15-phenyl-(22,25-dihydroxy)-ent-labda-8(17),13(E)-dieneis reported (2). These compounds were obtained by coupling via Electrophilic Aromatic Substitution (EAS) of 1,4-hydroquinone with primary or tertiary allyl alcohol derivatives of the natural ent-labdanes 3 and 4. With this new method, the best results were observed when mixtures of the primary alcohol derivatives 5-6 (26% yield of compound 1) and diol derivatives 9-10 (28% yield of compound 2) were used.
