RESUMO
A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1-26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility. Compound 23 was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound 23in vivo showed that it might be promising for the development of new antitumor agents.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Esterificação , Humanos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Triterpenos Pentacíclicos , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/uso terapêuticoRESUMO
Two new labdane diterpenoids, namely hedycoronals A and B (1 and 2, resp.), were isolated from the rhizomes of Hedychium coronarium, together with eight known diterpenoids, 4-11, and a known diarylheptanoid, 3. The structures of 1 and 2 were established by detailed interpretation of their 1D- and 2D-NMR spectra and HR-ESI-MS data. Inhibitory activities against human umbilical vein endothelial cells (HUMECs) proliferation and cytotoxic activities against four cancer cell lines were assessed for all the isolates. Most of these metabolites showed moderate or potent cytotoxic activities against four cancer cell lines. Moreover, compounds 3 and 8 exhibited promising inhibitory activities against HUMECs with the IC(50) values of 6.4 to 3.3â µM.