Table 2.
Structure-activity relationships of five OAK series, tested for their inhibitory activities with cultured human RBC infected with P. falciparum NF54d
| OAK group | OAK designation | Hb | Qc | IC50 (μM)a |
|---|---|---|---|---|
| 1 | C12K-1α4 | 50 | 2 | 2.1 |
| C12K-2α4 | 47.5 | 3 | >10 | |
| C12K-3α4 | 46.5 | 4 | >10 | |
| 2 | C12K-C6-α6 | 50 | 2 | 1 |
| C6-C6K-α12 | 42 | 2 | 5.6 | |
| C6-C6K-C6-α6 | 33 | 2 | >10 | |
| 3 | C12K-K-C6-α6 | 46 | 3 | >10 |
| C6-C6K-K-α12 | 38 | 3 | >10 | |
| C6-C6K-K-C6-α6 | 23 | 3 | >10 | |
| 4 | C12K-K -α12K | 48 | 4 | >10 |
| C12(ω7)K-K-α12K | 47 | 4 | >10 | |
| C12(ω7)K-K-α12 | 50 | 3 | 2.7 | |
| C12(ω7)K -α12K | 50 | 3 | 1.2 | |
| 5 | C12K-Kα10 | 49 | 3 | >10 |
| C12K-(Kα10)2 | 46 | 5 | >10 | |
| C12K-Kα8 | 47 | 3 | >10 | |
| C12-(Kα8)2 | 48.5 | 4 | >10 | |
| C12K-(Kα8)2 | 45 | 5 | 8.9 |
a
IC50 represents the peptide concentration that produced 50% inhibition of hypoxanthine uptake of P. falciparum after 18 h in culture.
b
H, hydrophobicity as determined by elution time in reversed-phase HPLC. Values were rounded to the nearest half-unit.
c
Q, molecular charge at physiological pH.
d
The most potent OAKs (IC50 of ∼1 μM) are highlighted in bold.