Harbinatic acid, a novel and potent DNA polymerase β inhibitor from Hardwickia binata

被引:23
作者
Deng, JZ
Starck, SR
Hecht, SM
Ijames, CF
Hemling, ME
机构
[1] Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA
[2] Univ Virginia, Dept Biol, Charlottesville, VA 22901 USA
[3] SmithKline Beecham Pharmaceut, Dept Phys & Struct Chem, King Of Prussia, PA 19406 USA
来源
JOURNAL OF NATURAL PRODUCTS | 1999年 / 62卷 / 07期
关键词
D O I
10.1021/np990099r
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Bioassay-guided fractionation of an active methyl ethyl ketone extract of Hardwickia binata, using an assay sensitive to DNA polymerase beta inhibition, resulted in the isolation of a potent inhibitor. This proved to be a novel diterpenoid, which has been named harbinatic acid (1). The structure of 1 was established as 3 alpha-O-trans-p-coumaroyl-7-labden-15-oic acid from spectroscopic analysis and by comparison with the published data for a structurally related compound. Compound 1 strongly inhibited calf thymus PNA polymerase beta, with an IC50 value of 2.9 mu M.
引用
收藏
页码:1000 / 1002
页数:3
相关论文
共 41 条
  • [11] FRIEDBERG EC, 1995, DNA REPAIR MUTAGENES
  • [12] FRIEDMAN HS, 1994, CANCER RES, V54, P3487
  • [13] Diterpenoids
    Hanson, JR
    [J]. NATURAL PRODUCT REPORTS, 1997, 14 (03) : 245 - 258
  • [14] Hanson JR, 1998, NAT PROD REP, V15, P93
  • [15] Chemistry of larixol I - Degradation of the side-chain and microbial hydroxylation
    Herlem, D
    Ouazzani, J
    KhuongHuu, F
    [J]. TETRAHEDRON LETTERS, 1996, 37 (08) : 1241 - 1244
  • [16] DNA-POLYMERASE-BETA BYPASSES IN-VITRO A SINGLE D(GPG)-CISPLATIN ADDUCT PLACED ON CODON-13 OF THE HRAS GENE
    HOFFMANN, JS
    PILLAIRE, MJ
    MAGA, G
    PODUST, V
    HUBSCHER, U
    VILLANI, G
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) : 5356 - 5360
  • [17] STRATEGIC DOWN-REGULATION OF DNA-POLYMERASE-BETA BY ANTISENSE RNA SENSITIZES MAMMALIAN-CELLS TO SPECIFIC DNA-DAMAGING AGENTS
    HORTON, JK
    SRIVASTAVA, DK
    ZMUDZKA, BZ
    WILSON, SH
    [J]. NUCLEIC ACIDS RESEARCH, 1995, 23 (19) : 3810 - 3815
  • [18] Taurospongin A, a novel acetylenic fatty acid derivative inhibiting DNA polymerase beta and HIV reverse transcriptase from sponge Hippospongia sp.
    Ishiyama, H
    Ishibashi, M
    Ogawa, A
    Yoshida, S
    Kobayashi, J
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (12) : 3831 - 3836
  • [19] LEE IS, 1995, TETRAHEDRON, V51, P21
  • [20] Investigation of the role of diterpenes produced by marine pulmonates Trimusculus reticulatus and T-conica
    Manker, DC
    Faulkner, DJ
    [J]. JOURNAL OF CHEMICAL ECOLOGY, 1996, 22 (01) : 23 - 35