The anti-neoplastic activity of ethylamine-carboxyborane and triphenylphosphine-carboxyborane in L-1210 lymphoid leukemia cells

✍ Scribed by Iris H Hall; E Stacy Hall; L K Chi; M C Miller Iii; Ken F Bastow; A Sood; B F Spielvogel

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 790 KB
• Volume: 6
• Category: Article
• ISSN: 0268-2605
• DOI: 10.1002/aoc.590060218

✦ Synopsis

Studies on the mode of action of two boroncontaining anti-neoplastic agents, ethylaminecarboxyborane and triphenylphosphinecarboxyborane, are reported. The major site of inhibition was in the pyrimidine de AOUO synthetic pathway at orotidine monophosphate decarboxylase activity. Additional sites which may facilitate the inhibition of cell growth were IMP dehydrogenase, thymidine kinase, TMP kinase and TDP kinase, m-RNA, r-RNA and t-RNA polymerase activities as well as topoisomerase I1 activity. The reduction in enzyme activities led to sufficient reduction of d(NTP) levels to suppress DNA synthesis and cell growth. DNA strand scission was evident in the presence of drug. Multiple modes of action are common with amine-carboxyboranes. Acute toxicity studies in mice showed that both agents were safe in their therapeutic range based on organ weights, histological tissue sections, clinical chemistry values and hematopoietic parameters .