ANTI-TUMOR AGENTS .34. MECHANISM OF ACTION OF BRUCEOSIDE-A AND BRUSATOL ON NUCLEIC-ACID METABOLISM OF P-388 LYMPHOCYTIC-LEUKEMIA CELLS

被引:46
作者
HALL, IH
LEE, KH
EIGEBALY, SA
IMAKURA, Y
SUMIDA, Y
WU, RY
机构
[1] Division of Medicinal Chemistry, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
关键词
Antineoplastic agents—bruceoside A and brusatol; effect on cultured P‐388 lymphocytic leukemia cell nucleic acid metabolism; Leukemia; lymphocytic—in vitro P‐388 cells; effect of quassinoids on nucleic acid metabolism; Nucleic acid synthesis; tumor—effect of quassinoids on P‐388 lymphocytic leukemia cells; Quassinoids—antineoplastic activity;
D O I
10.1002/jps.2600680726
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The quassinoids bruceantin, brucein D, brucein E, bruceoside A, and brusatol significantly inhibited P‐388 lymphocytic leukemic cell RNA and protein synthesis in tissue culture. However, DNA synthesis inhibition seemed to correlate more directly with the antineoplastic activity of these compounds in the in vivo P‐388 survival system. In vitro, brusatol and bruceoside A marginally inhibited 10‐day P‐388 lymphocytic leukemia DNA polymerase, RNA polymerase, thymidylate synthetase, dihydrofolate reductase, phosphoribosyl pyrophosphate aminotransferase, and cathepsin protease activities. In vivo studies demonstrated similar inhibition and elevated cyclic AMP levels, correlating positively with the antineoplastic activity of individual compounds. Purine synthesis was inhibited drastically by brusatol in vivo, and one key inhibition site in purine synthesis was at phosphoribosyl pyrophosphate aminotransferase, the regulatory enzyme. Histone phosphorylation and ribonucleotide reductase activity also were inhibited marginally by brusatol. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company
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页码:883 / 887
页数:5
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