TABLE 1
Properties of amantadine, HMA, and acylguanidine derivatives on H9N2 M2(WT) SAR investigation of analogs with activity against the S31 M2(WT)
Column 6 of this table shows cell survival determined from MTT assay.
| R | Compound | A/M2 WT (Mean ± S.D.) | Cell Survival MTT Assay | ||
|---|---|---|---|---|---|
| Inhibition by 100 μM (%) | IC50 (μM) | Estimated CC50 (µM) (N ≥ 3) | |||
| Amantadine | >99 | 0.6 ± 0.2 | >100 | ||
| HMA | >99 | 1.3 ± 0.3 | 4.7 ± 0.3 | ||
| BIT-225 | 30 ± 5 | ND | |||
| EIPA | 63 ± 2 | 52 ± 8 | |||
| BIT314 | 14 ± 2 | ND | |||
| M2WJ352 | <10 | ND | >100 | ||
 |  | 1 | >99 | 0.4 ± 0.1 | 4.9 ± 1.2 |
 | 1-Benzoylguanidine | <10 | ND | ||
 | 2 | 33 ± 8 | ND | ||
 | 3 | 33 ± 5 | ND | ||
 | 4 | >99 | 5.0 ± 1 | 5.9 ± 1.9 | |
 | 5 | 56 ± 2 | 50 ± 10 | 24 ± 8 | |
 | 6 | 33 ± 3 | ND | ||
 |  | 7 | <10 | ND | |
 |  | 8 | <10 | ND | |
 |  | 9 | >99 | 0.2 ± 0.1 | >100 |
 | 10 | <10 | ND | ||
 |  | 11 | >99 | 1.8 ± 0.1 | 55 ± 11 |
 |  | 12 | 38 ± 7 | ND | |
 |  | 13 | 16 ± 4 | ND | |
 | 14 | <10 | ND | ||
 | 15 | 36 ± 3 | ND | ||
| 26a | 20 ± 5 | ND | 25 ± 5 | ||
| 27a | >99 | 0.6 ± 0.1 | 55 ± 17 | ||
| 28a | <10 | ND | >100 | ||
CC50, 50% cytotoxic concentration; HMA, hexamethylene amiloride; ND, not determined; R, substitution.
↵a Structures are shown in Table 2.