RESUMO
Puerarin is a naturally occurring isoflavone and is frequently used for the treatment of cardiovascular symptoms in China. By the structural modification of the puerarin molecule at different positions, seven new puerarin derivatives were obtained, and their cardioprotective activities (in vitro and in vivo) were respectively evaluated. The finding that the activities of 3 and 8 markedly exceeded puerarin suggested that the acylated modification of phenolic hydroxyl at C-7 in the puerarin molecule may improve the cardioprotective activity, which will be an important reference for further structural optimization.
Assuntos
Cardiotônicos/síntese química , Cardiotônicos/farmacologia , Isoflavonas/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Cardiotônicos/química , Modelos Animais de Doenças , Isoflavonas/química , Estrutura Molecular , Ratos , Relação Estrutura-AtividadeRESUMO
AIM: To improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed. METHODS: These derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice. RESULTS: Twelve derivatives of camptothecin ester are new compounds. CONCLUSION: In vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.
Assuntos
Antineoplásicos/síntese química , Camptotecina/síntese química , Camptotecina/farmacologia , Neoplasias Hepáticas/patologia , Topotecan/análogos & derivados , Topotecan/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Camptotecina/química , Linhagem Celular Tumoral/efeitos dos fármacos , Ésteres/química , Feminino , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Transplante de Neoplasias , Topotecan/química , Topotecan/farmacologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A series of 7-acyloxymethylcamptothecin and 20-O-acyl-7-acyloxymethylcamptothecin derivatives were regioselectively prepared on different solvents. 7-Acyloxymethylcamptothecins possess more efficacy than 20-O-acyl-7-acyloxymethylcamptothecins against six human cancer cell lines in vitro.
