The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review)

  • Authors:
    • Yuki Matsui
    • Toshifumi Takeuchi
    • Yuko Kumamoto-Yonezawa
    • Masaharu Takemura
    • Fumio Sugawara
    • Hiromi Yoshida
    • Yoshiyuki Mizushina
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/etm_00000004
  • Pages: 19-26
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Abstract

Acetogenins from the Annonaceous plant are a fatty acid-derived natural product. Chemically synthesized natural acetogenins, such as mucocin (compound 1), jimenezin (compound 2), muconin (compound 4), pyranicin (compound 5) and pyragonicin (compound 6) were investigated. Concomitantly, 19-epi jimenezin (compound 3), 10-epi pyragonicin (compound 7) and a γ-lactone (compound 8), which is estimated to be a biosynthetic precursor of acetogenins, were synthesized and investigated. Compounds 5 and 6 strongly inhibited, and compound 7 moderately inhibited the activities of mammalian DNA polymerases (pols), such as replicative pol α and repair/recombination-related pol β and λ, and also inhibited human DNA topoisomerase (topos) I and II activities. On the other hand, compounds 1-4 and 8 did not influence the activities of any pols and topos. Compound 5 was the strongest inhibitor of the pols and topos tested, and the IC50 values were 5.0-9.6 µM, respectively. These compounds also suppressed human cancer cell growth with almost the same tendency as the inhibition of pols and topos. Compound 5 was the strongest suppressor of the proliferation of the promyelocytic leukemia cell line, HL-60, in human cancer cell lines tested with an LD50 value of 9.4 µM, and arrested the cells at G1 phases, indicating that it blocks DNA replication by inhibiting the activity of pols rather than topos. This compound also induced cell apoptosis. The relationship between the three-dimensional molecular structure of acetogenins and these inhibitory activities is discussed. The results suggested that compound 5 is a lead compound of potentially useful cancer chemotherapy agents.
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January-February 2010
Volume 1 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Matsui Y, Takeuchi T, Kumamoto-Yonezawa Y, Takemura M, Sugawara F, Yoshida H and Mizushina Y: The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) . Exp Ther Med 1: 19-26, 2010
APA
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., & Mizushina, Y. (2010). The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) . Experimental and Therapeutic Medicine, 1, 19-26. https://doi.org/10.3892/etm_00000004
MLA
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., Mizushina, Y."The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) ". Experimental and Therapeutic Medicine 1.1 (2010): 19-26.
Chicago
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., Mizushina, Y."The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) ". Experimental and Therapeutic Medicine 1, no. 1 (2010): 19-26. https://doi.org/10.3892/etm_00000004