INHIBITION OF THYMIDINE TRANSPORT INTO PHYTOHEMAGGLUTININ-STIMULATED LYMPHOCYTES BY TRITERPENOIDS FROM CIMICIFUGA SPECIES

Inhibitory effect of 24 triterpenoids from Cimicifuga spp. on lymphocyte blast-formation with phytohemagglutinin (PHA) was studied. The results of this study provided a structure-activity relationship for potent suppressive activities. A hemiacetal group in the side chain, an oxygenated group in the C12 position, a cyclopropane ring on the B ring and a double bond at the C7(8) position proved to be responsible for the activity. Cimicifugoside (I), which is endowed with all above mentioned functional groups to enhance the activity, was the strongest inhibitor of thymidine transport into PHA-stimulated lymphocytes. As little as 4 ng/ml cimicifugoside caused 50% inhibition of thymidine-3H uptake in the lymphocyte culture. Moreover, addition of the triterpenoid to mouse lymphosarcoma L-5178Y cell cultures resulted in a significant inhibition of transport of nucleosides into the cells, where neither cytotoxicity nor inhibition of the cell growth at higher concentration was observed. At same conditions, inhibitory activities of incorporation of leucine and glucosamine were not detected. These results indicate that the inhibition of thymidine uptake by cimicifugoside and its related compounds may not be due to the inhibition of DNA synthesis but on the membrane transport of nucleoside and/or nucleoside trapping mechanisms. © 1979, The Pharmaceutical Society of Japan. All rights reserved.