This work is an extension of our previous work (Hall et al., 1993) on
the synthesis and cytotoxic activity of boronated peptides. The aim of
this work was to carry out structural modifications of the amine term
inal in compounds 1 and 2, to increase water solubility, and its effec
t on the cytotoxicity to tumor cell lines. Surprisingly, only compound
s 4, 7 and 8 were more water soluble than the parent compounds. With t
he exception of compound 4, the new derivatives were generally less ef
fective than the parent compounds (1 and 2). There was no apparent cor
relation between structure and activity. Cytotoxic effect was more pro
nounced in single cell suspended cells. The growth of solid tumor cell
lines was not significantly reduced. The most active derivative, thyl
)-2-methylamino-2-oxoethyl]amino]carboxy]boron (4), inhibited DNA, RNA
, and protein synthesis in Tmolt(3) cells. Enzymsttic activities, e.g.
, DNA polymerase alpha, m-RNA polymerase, PRPP amidotransferase, carba
myl phosphate synthetase, TMP-kinase, TDP-kinase, dihydrofolate reduct
ase, and ribonucleoside reductase were reduced after 60 min incubation
with 4. d(TTP) and d(CTP) pool levels were also reduced by 60 min inc
ubation with 4.