Table 1.
In Vitro HDAC Inhibition (nM), Antilieshmanial (μg/mL) and Antimalarial (ng/mL) Activities of Aryltriazolylhydroxamates HDACi.
 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Compd | R | n | HDAC Inhibition IC50 (nM) | Antileshmanial Activity c | Antimalarial Activity c | Cytotoxicity (VERO) IC50 (ng/ml) | S. I. D6 (W2) | ||
| IC50 (μg/ml) ±SD | IC90 (μg/ml) ±SD | Plasmodium falciparum (D6 clone) IC50 (ng/ml) | Plasmodium falciparum (W2 clone) IC50 (ng/ml) | ||||||
| 15 |  |
3 | N.D. a | NA | NA | 2850 ±50 | 3500 ±800 | NC | >1.7 (>1.4) |
| 16 |  |
4 | 110.0 a | NA | NA | 125 ±5 | 120 ±10 | NC | >38.08 (>39.6) |
| 17 |  |
5 | 14.2 a | 17.5 ±0.71 | >40 | 88 ±2 | 130 ±30 | 3950 ±550 | 44.9 (30.4) |
| 18 |  |
6 | 9.6 a | 4.55 ±0.35 | 40.0 ±0.0 | 38 ±5 | 24.5 ±1.5 | 430 ±20 | 11.3 (17.6) |
| 19 |  |
7 | 363.6 | 17.75 ±0.35 | >40 | 645 ±55 | 695 ±115 | NC | >7.4 (>6.8) |
| 20 |  |
8 | 55.4 | 18.5 ±0.71 | >40 | 2650 ±450 | 2750 ±50 | 3350 ±550 | 1.9 (1.2) |
| 21 |  |
5 | 4.3 a | 15.5 ±0.71 | >40 | 68 ±8 | 38.5 ±1.5 | 3400 ±200 | 50.0 (88.3) |
| 22 |  |
6 | 106.1 a | 5.35 ±0.35 | 36.0 ±1.41 | 24.5 ±5.5 | 32 ±13 | 765 ±35 | 31.2 (23.9) |
| 23 |  |
7 | 15.9 | 24.0 ±2.83 | >40 | 175 ±105 | 185 ±15 | 970 ±130 | 3.8 (3.6) |
| 24 |  |
8 | 596.6 | 20.75 ±0.35 | >40 | 1800 ±500 | 1650 ±50 | NC | >2.6 (>2.9) |
| 25 |  |
5 | 287.2 a | 11.45 ±3.61 | >40 | 175 ±45 | 205 ±55 | NC | >27.2 (>23.2) |
| 26 |  |
6 | 365.8 | 15.5 ±0.71 | 40 | 75.5 ±21.5 | 81 ±49 | 3780 ±980 | 50.1 (46.7) |
| 27 |  |
7 | 425.8 | 19.75 ±0.35 | >40 | 1495 ± 253 | 1687± 321 | NC | >3.2 (>2.8) |
| 28 |  |
5 | 112.5 a | 17.75 ±0.35 | >40 | 195 ±65 | 132.5 ±57.5 | NC | >24.4 (>35.9) |
| 29 |  |
5 | 67.6 a | 20.5 ±0.71 | >40 | 985 ±15 | 625 ±95 | 2900 ±300 | 2.9 (4.6) |
| 30 |  |
6 | 23.9 a | 5.75 ±0.35 | 40.0 ±0.0 | 69 ±1 | 40 ±5 | 950 ±150 | 13.8 (23.8) |
| 31 |  |
5 | 43.4 a | 21.5 ±2.12 | >40 | 130 ±40 | 140 ±40 | 3850 ±650 | 29.6 (27.5) |
| 32 |  |
5 | 31.9 a | 17.0 ±1.41 | >40 | 79.5 ±0.5 | 68 ±8 | 2700 ±300 | 34.0 (39.7) |
| 33 |  |
5 | 17.4 a | 23.0 ±1.41 | >40 | 1250 ±50 | 1950 ±750 | 3300 ±700 | 2.6 (1.7) |
| 34 |  |
6 | 2.8 | 26.0 ±0.0 | 40 | 120 ±20 | 140 ±20 | 710 ±210 | 5.9 (5.1) |
| 35 |  |
5 | 2.1 a | 18.5 ±0.71 | >40 | 130 ±6 | 90 ±10 | 2350 ±850 | 18.1 (26.1) |
| 36 |  |
5 | 13.9 a | NA | NA | NA | NA | NC | - |
| 37 |  |
5 | 76.0 a | 18.75 ±0.35 | >40 | 150 ±10 | 97.5 ±2.5 | 2300 ±500 | 15.3 (23.6) |
| 38 |  |
5 | 315.9 a | 40 | >40 | 2000 ±300 | 2600 ±200 | NC | >2.4 (>1.8) |
| 39 |  |
5 | 31.7 a | 11.5 ±0.71 | >40 | 46 ±6 | 36.5 ±13.5 | NC | >103 (>130) |
| 40 |  |
5 | 1.9 a | 11.25 ±0.35 | 32.5 ±0.71 | 37.5 ±17.5 | 26 ±4 | NC | >127 (>183.1) |
| 41 |  |
6 | 5.4 a | 20.5 ±0.71 | >40 | 25 ±5 | 25 ±5 | NC | >190.4 (>190.4) |
| 42 |  |
7 | 108.9 | 20.25 ±0.35 | 40 | 840 ±40 | 650 ±50 | NC | >5.6 (>7.3) |
| 43 |  |
8 | 147.7 | 20.0 ±0.0 | 40.0 ±0.0 | 3350 ±150 | 3200 ±200 | NC | >1.4 (>1.5) |
| 44 |  |
5 | 162.6 a | 13.0 ±2.83 | 38.0 ±0.0 | 2100 ±800 | 2600 ±100 | 2700 ±200 | 1.3 (1.0) |
| 45 |  |
5 | 2.3 a | 28.0 ±2.83 | >40 | 45.5 ±9.5 | 47.5 ±22.5 | NC | >104.6 (>100.2) |
| 46 |  |
6 | 16.6 a | NA | NA | 1150 ±150 | 1250 ±50 | NC | >4.1 (>3.8) |
| 47 |  |
7 | 212.9 | NA | NA | 88.5 ±6.5 | 127.5 ±2.5 | 3850 ±650 | 43.5 (30.2) |
| 48 |  |
5 | 1.8 a | 18.0 ±2.83 | >40 | 35 ±5 | 31 ±11 | 2850 ±50 | >81.4 (>91.9) |
| 49 |  |
6 | 15.3 a | 18.5 ±2.12 | >40 | 47.5 ±4.5 | 53 ±13 | 2650 ±350 | 55.8 (50.0) |
| 50 |  |
7 | 226.1 | NA | NA | 112 ±13 | 165 ±35 | 650 ±250 | 5.8 (3.9) |
| 51 |  |
5 | 2.1 a | 9.5 ±0.71 | 39.0 ±1.41 | 33 ±3 | 34 ±16 | 2400 ±400 | 72.7 (70.6) |
| 52 |  |
5 | 151.5 a | 18.5 ±0.71 | >40 | 52.5 ±12.5 | 33 ±3 | NC | >90.7 (>144.2) |
| Chloroquine | - | NT | NT | NT | 17 | 125 | NT | NT | |
| Artemisinin | - | NT | NT | NT | 4 | 6 | NT | NT | |
| Pentamidine | - | NT | 0.90 ±0.9 | 1.80 ±0.0 | NT | NT | NT | NT | |
| Amphotericine B | - | NT | 0.14 ±0.01 | 0.31 ±0.01 | NT | NT | NT | NT | |
| SAHA | - | 65 | 29.7 ±5.4 | 57.9± 6.8 | 261.6 ± 39.5 | 478.9± 33.4 | 1200 | 4.8 (2.5) | |
| TSA | - | 5 | 1.37± 0.16 | 20.5 ±0.71 | 41.2 ± 6.1 | 49.5 ± 7.4 | 95 | 2.6 (2.2) | |
a
Each value is obtained from three independent experiments
b
Cited from ref. 17
c
Values are mean ± SD of triplicates NA = Not active up to the highest concentration tested NC = No cytotoxic up to highest concentration tested NT = Not tested