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. Author manuscript; available in PMC: 2011 Jan 15.
Published in final edited form as: Bioorg Med Chem. 2009 Dec 26;18(2):953. doi: 10.1016/j.bmc.2009.11.029

Table 2.

Inhibition concentrations (IC50, µM) against isolated DHFRa and selectivity ratiosb.

Compound P. carinii rat liver rl/pcb T. gondii rl/tgb M. avium rl/mab
5 0.078 20.5 262.8 12 1.7 0.00973 2106.9
6 8.6 >83 >10 >83 NDc
7 >12 >12 ND >12 ND
8 20(27%)d 196(41%) ND 19.7 ND 196(20%) ND
9 60 14.4 0.2 25.5 0.6 56.2 0.26
10 24 42.2 1.8 38.4 1.1 61.9 0.68
11 34.7 61.9 1.8 69.4 0.9 25.5 2.43
12 31(39%) 39.1 ND 81.8 0.5 31(8%) ND
13 20.3 55.6 2.7 44.2 1.3 23.9 2.33
14 25.2 51.3 2.0 45.9 1.1 28.4 1.81
15 36.4 66.6 1.8 51.7 1.3 16.3 4.09
16 36.5 24.3 0.7 16.2 1.5 23.4 1.04
TMQ 0.042 0.003 0.07 0.010 0.3 0.0015 2.0
TMP 12 180 14 2.8 65 0.3 610
a

These assays were carried out at 37 °C under conditions of saturation with substrate (90 µM dihydrofolic acid) and cofactor (119 µM NADPH) in the presence of 150 mM KCl.

b

Selectivity ratios, rl/pc = IC50 rat liver dihydrofolate reductase/ IC50 P. carinii dihydrofolate reductase; rl/tg = IC50 rat liver dihydrofolate reductase/ IC50 T. gondii dihydrofolate reductase; rl/ma = IC50 rat liver dihydrofolate reductase/ IC50 M. avium dihydrofolate reductase.

c

ND = not determined.

d

Number in parenthesis indicate the percentage inhibition at the given concentration