RESUMO
Eight new emodin derivatives that contain large conjugative system have been synthesized and their anticancer activities also have been evaluated. The result shows that large conjugative system can not enhance the anticancer activities of emodin derivatives, but the introduction of an alkylating center can make emodin derivative effective against cancer cell lines. Compound 12 has the highest alkylating ability, but its anticancer activity is not remarkable, which indicates that there is not a direct correlation between the chemical reactivity of the alkylating agent and the toxic effects.
Assuntos
Antineoplásicos/síntese química , Emodina/análogos & derivados , Emodina/síntese química , Antineoplásicos/farmacologia , Antineoplásicos Alquilantes/síntese química , Antineoplásicos Alquilantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Emodina/farmacologia , Humanos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
<p><b>OBJECTIVE</b>To screen a group of traditional Chinese medicines with effect on pregnane X receptor (PXR)-mediated transcription regulation of P450 3A4 (CYP3A4); and to study whether they can induce the expression of CYP3A4 with a dose, time-dependent manner.</p><p><b>METHOD</b>Transient cotransfection reporter gene assays were performed with pCI-hPXR-neo, pGL3-CYP3A4-Luc and beta-galactosidase expression plasmid in HepG2 cells.</p><p><b>RESULT</b>Rhizoma Curcumae, Atractylodes lancea, A. macrocaphala and Poria cocos could induce transcriptional expression of CYP3A4. In the dose-effect study, 24 h after induction, 500 mg x L(-1) Rhizoma Curcumae, A. lancea, A. macrocaphala and Poria cocos, respectively, could induce the CYP3A4 gene expression with (6.82 +/- 0.09), (6.76 +/- 0.20), (5.49 +/- 0.13) and (4.97 +/- 0.07) folds, as compared with 0.1% DMSO treated cells. In the time-effect study, 500 mg x L(-1) Rhizoma curcumae, A. lancea, A. macrocaphala and Poria cocos for 48 h could induce the CYP3A4 gene expression with (7.74 +/- 0.54), (7.34 +/- 0.10), (5.54 +/- 0.11) and (5.32 +/- 0.18) folds, compared with 0.1% DMSO treated cells.</p><p><b>CONCLUSION</b>Rhizoma Curcumae, A. lancea, A. macrocaphala and Poria cocos could induce the expression of CYP3A4 gene transcription through activating PXR.</p>