RESUMO
Here, we synthesized three acetogenin analogs containing pyrimidine moieties linked by amine bonds, which represent the skeleton structure of pyrimidifen, a mitochondrial complex I-inhibiting insecticide. Replacing the pyrimidine moiety linked by the amine bond remarkably enhanced growth-inhibitory activity of the analogs against several human cancer cell lines. Moreover, these analogs selectively and potently inhibited the growth of these human cancer cell lines regardless of the pyrimidine substituents. Furthermore, COMPARE analyses suggested that these analogs inhibited cancer growth by inhibiting mitochondrial complex I. Our study provides insights into the design of acetogenin analogs as novel antitumor agents.
Assuntos
Antineoplásicos , Neoplasias , Humanos , Acetogeninas , Aminas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Pirimidinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Proliferação de Células , Estrutura MolecularRESUMO
The absolute configuration was determined for the title compound, (-)-C(32)H(56)O(6)S(2)Si, (I), which was prepared in a synthetic study on the natural products bryostatins. Two independent molecules show similar conformations, except for the orientation of the methoxy groups.
RESUMO
The absolute configuration was determined for the title compound, (+)-C(18)H(24)O(3)S, (I), which was prepared in a synthetic study on the natural products, bryostatins.