Cytotoxicity and mode of action of aliphatic dicarboxylic acids in L1210 lymphocytic leukemia cells.
The aliphatic dicarboxylic acid surprisingly afforded potent cytotoxicity and in vivo antineoplastic activity. The agents were active against the growth of a variety of leukemias, lymphomas, and suspended HeLa uterine carcinoma. Suppression of growth of cell lines derived from human solid cancers, e.g. SW-480 colon adenocarcinoma, lung MB- 9812, glioma HS-683, and rat osteosarcoma UMR-106 was observed. A mode of action study in L1210 lymphoid leukemia demonstrated that DNA and RNA syntheses were inhibited at multiple sites including ribonucleoside reductase, purine de novo synthesis at PRPP-amidotransferase and IMP dehydrogenase and nucleic acid kinases. These studies could not exclude the possibility that the agents also interacted with the DNA molecule itself interfering with the utilization of the template.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Izydore
R A
RA
Warren
A E
AE
Barnes
C R
CR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007939:Leukemia L1210; D008297:Male; D051379:Mice; D051381:Rats
D000970:Antineoplastic Agents; D003998:Dicarboxylic Acids; D004247:DNA