Table 2

Physicochemical properties of boronated dThds and their in vitro cytotoxicity data in L929 and CCRF-CEM wild-type cell lines and their TK1 deficient sub lines

CompoundPhysicochemical Property Log P (HPLC) *IC50 values for mammalian cell lines (μmol/L)
L929 §CCRF-CEM §
Wild-typeTKWild-typeTK
1 1.872142 ± 6>16050 ± 755 ± 8
2 1.847>160>16057 ± 746 ± 18
3 2.147119 ± 7134 ± 643 ± 344 ± 3
4 2.44556 ± 9127 ± 555 ± 1851 ± 20
5 2.95439 ± 837 ± 429 ± 925 ± 5
6 3.22620 ± 517 ± 416 ± 513 ± 6
7 1.468>160>160127 ± 8126 ± 3
8 1.27>160>16096 ± 489 ± 7
9 1.522>160>160102 ± 790 ± 9
10 2.087113 ± 11>16043 ± 1746 ± 18
11 2.41167 ± 663 ± 639 ± 1026 ± 5
12 2.60638 ± 556 ± 339 ± 1430 ± 13
  • * Log P values were determined by HPLC as described in Materials and Methods.

  • Cell growth inhibition data are expressed as mean ± SDs of three experiments, each performed in triplicate. Cells were incubated with compounds 1-12 for 72 hours and cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as described in Materials and Methods.

  • The IC50 value (μmol/L) is defined as the concentration of the compound that inhibited cell growth by 50% following 72 hours of incubation.

  • § The TK-specific activities in L929 and CCRF-CEM wild-type strains were 227 ± 16 and 202 ± 15 pmol/min/mg total proteins, respectively, whereas in strains lacking TK1, the activities were 9 ± 3 and 5 ± 1 pmol/min/mg total proteins, respectively. Data represent the mean ± SDs of three independent experiments.