The Synthesis and Antitumor Activity of the Sodium Salt and Copper (II) Complex of N-[(Trimethylamineboryl)-Carbonyl]-L-Phenylalanine Methyl Ester

Abstract

Sodium N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine 2 and {N-[(trimethylamineboryl)-carbonyl]-L-phenylalanyl- carbxylato}-bis-{N-[(trimethylaminebryl)-carbonyl]-L-phenylalanine} dicopper (II) 3 were successfully synthesized. The agents blocked L1210 leukemic cell DNA and RNA syntheses by inhibiting multiple enzyme activities for nucleic acid synthesis, e.g. PRPP amido transferase, IMP dehydrogenase, DNA polymerase α, thymidine kinase, and TMP kinase. The copper (II) complex 3 demonstrated improved ability to inhibit L1210 partially purified DNA topoisomerase II compared to the parent compound while the sodium salt was inactive at 100 μM.