ガマ毒 bufadienolide の構造とヒト肝癌由来細胞 PLC/PRF/5 に対する殺細胞活性

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"The toad poison bufadienolides having novel steroidal A/B cis and C/D cis structure exhibit a variety of biological activities. To carry out systematic studies on the biological activities of the chinese traditional crude drug ""Senso"" (Ch' an Su), we investigated its cytotoxicities against cell line of human liver cancer PLC/PRF/5. Our research was extended to studies on relationship the bufadienolide structures and PLC/PRF/5 activities, since the extracts of Ch' an Su and the major bufadienolide showed strong activity for PLC/PRF/5. Natural bufadienolide exhibited a potent cytotoxicity against PLC cell than their isomers and related compounds. Hellebrigenin was most active (IC_<50> 1.6×10^<-4>μg/ml). Other compound at 10^<-4>μg/ml level were bufalin-3-acetate, gamabufotalin, bufalin, sillarenin, bufotalin, telocinobufagin, bufalin-3-succinate-tert-butylcarbazoate, cinobufagin, bufalin-3-suberate, desacetyl-bufotalin and digitoxigenin. The 14β-hydroxy derivatives showed the higher activities than 14β, 15β-epoxy, 14α, 15α-epoxy and α-pyrone ring opening compounds (Table 2). We discussed about (1) activities for the colchicine-treated cells (Table 2), (2) dependence of activity with concentration of compounds (Fig. 1) and (3) characterization of activity on classification of compoumds (Fig. 2). On the other hand, the bufadienolides and related compounds were classified into the five groups, A∿E. Relationship between structure and activity on each group was discussed in section III. Importance of both D ring structures and 3-substituent structures was found. As a summary, on the relationship between structures and activities, the effects of substitution to the model compounds, e. g. bufalin and resibufogenin were discussed and the results were shown in Table 9 and 10. The most important factors were found to be the α-pyrone ring, 14β-OH or 14β, 15β-epoxy, 19-CHO, 11α-OH and 16β-OAc groups. Activities of cardenolides were more week than those of bufadienolide. In general, the C/D cis compounds showed higher activity than the C/D trans ones. Finally, we discuss about the antineoplastic activities of bufadienolides such as cell line of the KB and HeLa-S3,and the P388 and L1210 lymphocytic leukemia, in the comparison with PLC/PRF/5 activities, in Section IV (Table 11). A tendency of results was similar to those of the anaesthetic action and antiviral activity."
神奈川大学の論文

ガマ毒 bufadienolide の構造とヒト肝癌由来細胞 PLC/PRF/5 に対する殺細胞活性

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