Effect of pisiferic acid and its derivatives on cytotoxicity macromolecular synthesis and DNA polymerase alpha of HeLa cells

Int J Biochem. 1989;21(5):463-8. doi: 10.1016/0020-711x(89)90125-0.


1. Seventy-seven derivatives of pisiferic acid (2), an antimicrobial diterpenoid, were tested for cytotoxicity against HeLa cells and 9 derivatives were found to show cytotoxicity at less than 2 micrograms/ml dose (IC50). 2. Hydrophobicity was revealed to be an important factor for cytotoxicity of the derivatives. 3. Compound 2 inhibited predominantly DNA synthesis in HeLa cells as compared with RNA and protein synthesis. 4. No direct interaction between 2 and nucleic acid bases was indicated by a u.v. spectral method. 5. Several of the pisiferic acid species showed inhibitory action on HeLa DNA polymerase alpha, and the inhibitory activity was about 1/20 of aphidicolin.

Publication types

  • Comparative Study

MeSH terms

  • Cell Survival / drug effects
  • DNA / biosynthesis
  • DNA Polymerase II / metabolism*
  • Diterpenes / pharmacology*
  • HeLa Cells
  • Humans
  • Nucleosides / metabolism
  • Protein Biosynthesis
  • RNA / biosynthesis
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship


  • Diterpenes
  • Nucleosides
  • RNA
  • pisiferic acid
  • DNA
  • DNA Polymerase II