Effect of pisiferic acid and its derivatives on cytotoxicity macromolecular synthesis and DNA polymerase alpha of HeLa cells.
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.
Kobayashi
K
K
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Kuroda
K
K
Shinomiya
T
T
Nishino
C
C
Ohya
J
J
Sato
S
S
D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004257:DNA Polymerase II / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009705:Nucleosides / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D004224:Diterpenes; D009705:Nucleosides; D012313:RNA; C060710:pisiferic acid; D004247:DNA; D004257:DNA Polymerase II