Syntheses And Anticancer Activities Of New Ethisterone Induced Silver(?) Complexes

Objective Our aim is to prepare amino acid-ethisterone schiff base derivative and their silver complexes by ethisterone as raw materials and study their antitumor activities for hepatoma carcinoma cell.It will be summarized for the effects of groups and introduced silver ions on their antitumor activities.The new silver(I)-ethisterone complexes will be screened with exellent antitumor activities.Methods Novel amino acid-ethisterone schiff base derivative and their silver complexes have been prepared by organic phase method;Novel compounds were characterized by the method of X-ray diffraction,IR,UV,NMR spectroscopy and elemental analysis;Anticancer activity in vitro of novel compounds have been studied by MTT method.Results One chiral silver cluster complex(Ag10-L1),ten types of ethisterone derivatives(Ln)and their silver complexes(Ag-Ln)have been successfully prepared.As for inhibitory effect on HepG2 cells,ethisterone derivatives show limited improvements as compared to their ethisterone precursor,the rate of tumor inhibition are 19%,13%,9%,8%,9%,8%,18%,13%,8%,22%,respectively.Ten Ag-Ln complexes also show limited enhancement of antitumor activity,the rate of tumor inhibition are 28%,30%,30%,25%,22%,20%,31%,40%,26%,40%,respectively.However,Ag10-L1 shows significant inhibitory activity with the IC50 values as 560 nM and 165 nM for CCC-HEL-1 and HepG2 cells,respectively.Ag10-L1 displays 3.4-fold higher in vitro cytotoxicity to HepG2 cells than that of the normal CCC-HEL-1 cells.Conclusions The lower enhancement of antitumor activity of amio-acid modifed ethisterone has been observed,while the introduction of silver ions shows a little higher enhancing activity for HepG2 cells.Chiral silver cluster complex not only present significant inhibitory effect on HepG2 cells,but also possess better targeting activity.The successful preparation of silver(I)-ethisterone clusters not only provides new structure models for the study of clinical antitumor drugs,but also opens a new strategy for design and synthesis of novel silver(I)-medicine complexes.