Antitumor agents 68: effects of a series of helenalin derivatives on P-388 lymphocytic leukemia nucleic acid and protein synthesis.
A series of analogues related to helenalin demonstrated moderate capability for inhibiting the growth of murine P-388 lymphocytic leukemia cells in vivo and in vitro. The growth inhibition correlated with suppression of both DNA and protein synthesis in P-388 cells. The inhibition of protein synthesis occurred at a relatively low concentration and appeared to occur at the level of initiation. The suppression of DNA synthesis in P-388 cells correlated positively with inhibition of inosine 5'-monophosphate dehydrogenase activity. Although nuclear and alpha DNA polymerase activities were suppressed by certain analogues, the inhibition of the polymerases did not correlate positively with DNA synthesis inhibition and, furthermore, the magnitude of suppression of DNA polymerase activity did not appear to be sufficient to account for the observed suppression of DNA synthesis in P-388 cells.
Hall
I H
IH
Williams
W L
WL
Chaney
S G
SG
Gilbert
C J
CJ
Holbrook
D J
DJ
Muraoka
O
O
Kiyokawa
H
H
Lee
K H
KH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007941:Leukemia P388 / Q000201:enzymology / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D019384:Nucleic Acid Synthesis Inhibitors; D011687:Purines / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011687:Purines; D012334:RNA, Neoplasm; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C001329:helenalin; D007168:IMP Dehydrogenase