Table 3.
Activity of 41F5-derived antifungals with bicyclic ring systems at the 5-position
|
H. capsulatum |
C. neoformans (H99 strain) |
P388D1 | SI (Hc) |
SI (Cn) |
||||
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| Cmpd | R1 | R2 | IC50 (µM) [±SD] |
MIC (µM) |
IC50 (µM) [±SD] |
MIC (µM) |
IC50 (µM) [±SD] |
||
| A |
|
|
0.60 [±0.03] | 1.25 | > 20 | > 40 | 27.59 [±4.12] | 46 | nd |
| 41F5 |
|
|
0.48 [±0.01] | 1.25 | 0.67 [±0.06] | 1.25 | > 40 | > 83 | > 60 |
| 17a |
|
|
0.92 [±0.38] | 5.00 | > 20 | > 40 | 18.87 [±3.05] | 21 | nd |
| 17b |
|
|
0.20 [±0.01] | 0.31 | 0.34 [±0.04] | 0.63 | > 40 | > 200 | > 118 |
| 20a |
|
|
> 20 | > 40 | > 20 | > 40 | nd | nd | nd |
| 20b |
|
|
1.54 [±0.42] | 2.50 | 1.52 [±0.22] | 5.00 | > 40 | > 26 | > 26 |
| 21a |
|
|
0.40 [±0.01] | 0.63 | > 20 | > 40 | 17.75 [±5.00] | 44 | nd |
| 21b |
|
|
0.42 [±0.01] | 1.25 | 0.62 [±0.12] | 2.50 | > 40 | > 95 | > 65 |
| 22a |
|
|
0.20 [±0.01] | 0.31 | > 20 | > 40 | > 40 | > 200 | nd |
| 22b |
|
|
0.20 [±0.01] | 0.31 | 0.37 [±0.09] | 1.25 | > 40 | > 200 | > 108 |
| 23a |
|
|
0.27 [±0.02] | 0.63 | > 20 | > 40 | 16.90 [±1.75] | 63 | nd |
| 23b |
|
|
> 20 | > 40 | > 20 | > 40 | nd | nd | nd |
| 24 |
|
|
> 20 | > 40 | > 20 | > 40 | nd | nd | nd |
| 26a |
|
|
0.38 [±0.02] | 0.63 | > 20 | > 40 | > 40 | > 105 | nd |
| 26b |
|
|
0.25 [±0.02] | 0.63 | 0.41 [±0.07] | 1.25 | > 40 | > 160 | > 98 |
| 27a |
|
|
0.90 [±0.29] | 2.50 | > 20 | > 40 | 24.27 | 27 | nd |
| 27b |
|
|
> 20 | > 40 | > 20 | > 40 | nd | nd | nd |
| 28a |
|
|
> 20 | > 40 | > 20 | > 40 | nd | nd | nd |
| 28b |
|
|
3.05 [±0.25] | 10.00 | 3.24 [±0.42] | 10.00 | 13.92 [±1.19] | 5 | 5 |
| 36a |
|
|
0.64 [±0.03] | 1.25 | > 20 | > 40 | > 40 | > 63 | nd |
| 36b |
|
|
0.19 [±0.01] | 0.31 | 0.89 [±0.32] | 2.50 | > 40 | > 211 | > 45 |
SD: Standard deviation; SI: Selectivity index. Not determined