Synthesis of 1, 8-diacetyl rhein (2-bromo)-ethyl ester and its role in osteosarcoma MG-63 cells / 中国药理学通报

ABSTRACT

Aim To design and synthesize of a new rhein derivative 1 , 8-diacetyl rhein ( 2-bromo )-ethyl ester ( rhein derivatives B ) and explore its effect on os-teosarcoma MG-63 cells and the related mechanism . Methods 1 , 8-diacetyl rhein ( 2-bromo )-ethyl ester was synthesized from rhein and its structure was identi-fied by UV, IR and NMR spectra .The purity of the synthetic product was determined by HPLC .The in vitro anti-proliferative activity of rhein and the synthetic product on osteosarcoma MG-63 cells were determined by MTT assay .Apoptosis and cell cycle distribution were detected by flow cytometry .Results The molec-ular structure of 1 , 8-diacetyl rhein ( 2-bromo )-ethyl ester was confirmed by UV , IR, 1 H NMR and 13 C NMR, and the purity was higher than 98％.The IC50 values of rhein and rhein derivatives B on osteosarcoma MG-63 cells were 110.60μmol· L-1 and 25.78μmol · L-1 , respectively .The Results of flow cytometry showed that the apoptotic rates of rhein and rhein de-rivatives B at the concentration of 80 μmol· L-1 were (6.87 ±0.53)％and (48.84 ±2.20)％, respective-ly, and the cell cycle was mainly arrested in S phase on MG-63 cells.Conclusions The anti-tumor activity of 1,8-diacetyl rhein-(2-bromo)-ethyl ester is superior to that of rhein in vitro, and the mechanisms may be associated with blocking the process of cell cycle of os-teosarcoma MG-63 cells and initiating apoptosis .