TABLE 2.
Effect of exogenous folate supplementation on the in vitro inhibitory activity of antifolates against P. falciparum 3D7 adapted to continuous culture in folate and pABA free media
IC50 values obtained from 3D7 parasites were cultured in either dialyzed media (folate-free RPMI-1640 and dialyzed serum) or “free” media (folate- and pABA-free RPMI-1640 and Albumax II). Folate supplements were present at the following concentrations: for dialyzed media, 7.3 μm pABA and 2.3 μm for both 5-MTHF and FA; for free media, 150 nm pABA, 25 nm 5-MTHF, and 0.5 nM FA. Values represent the mean ± S.D. and n = 4–7. In all comparisons between free and dialyzed media there was a statistical difference (p < 0.0001, t test), with the values observed with dialyzed media always higher than the folate-free media. pABA significantly antagonized antifolate activity under both sets of culture conditions for both SDX and PYR (p < 0.05), whereas 5-MTHF had no effect, and FA was only significant with SDX in dialyzed media (p < 0.05).
| Supplements | IC50 values |
|||
|---|---|---|---|---|
| SDX |
PYR |
|||
| Dialyzed | Free | Dialyzed | Free | |
| μm | nm | nm | pm | |
| Control | 426.13±85.46 | 26.15±12.13 | 50.10±11 | 0.5±0.05 |
| pABA | 1952.33±189.98 | 572.43±145.36 | 90.2±12 | 41.86±3.11 |
| 5-MTHF | 472.25±42.11 | 23.28±15.29 | 70.3±09 | 0.39±0.06 |
| FA | 1572.06±413.66 | 33.15±22.23 | 100.4±30 | 0.36±0.06 |