Table 2. In Vitro Cytotoxicity and Trypanocidal Activity of Nitrofuryl- (1a–9a) and Nitrothienylazines (1b–9b)e.
| reference drug/compound # | cytotoxicityCC50 ± SD(μM)a |
trypanocidal activityIC50 ± SD(μM)b(SI)c |
|||||
|---|---|---|---|---|---|---|---|
| MDBK | Tbb GuTat3.1 | Tbg IL1922 | Tbr IL1501 | Teq IVM-t1 | Tev Tansui | Tc IL3000 | |
| Nitrofurantoin | |||||||
| 73.02 ± 36.15 | 1.51 ± 0.03 (48) | 1.85 ± 0.23 (39) | 1.69 ± 0.20 (43) | 1.45 ± 0.03 (50) | 1.67 ± 0.07 (44) | 0.42 ± 0.05 (174) | |
| Nitrofurylazines | |||||||
| 1a | 11.59 ± 1.52 | 3.94 ± 2.08 (3) | 4.00 ± 1.11 (3) | 4.00 ± 1.09 (3) | 3.49 ± 1.89 (3) | 3.71 ± 2.04 (3) | 0.19 ± 0.08 (61) |
| 2a | 33.92 ± 22.17 | 2.03 ± 0.95 (17) | 2.48 ± 0.67 (14) | 2.42 ± 0.40 (14) | 2.46 ± 0.70 (14) | 2.66 ± 1.02 (13) | 0.18 ± 0.07 (188) |
| 3a | >360.15 | 1.02 ± 0.43 (>353) | 1.20 ± 0.24 (>300) | 1.26 ± 0.15 (>286) | 1.18 ± 0.17 (>305) | 1.78 ± 0.46 (>202) | 0.14 ± 0.05 (>2 572) |
| 4a | >310.45 | 0.76 ± 0.35 (>408) | 0.81 ± 0.20 (>383) | 0.86 ± 0.23 (>361) | 0.71 ± 0.18 (>437) | 1.15 ± 0.16 (>270) | 0.04 ± 0.01 (>7 761) |
| 5a | >388.74 | 3.25 ± 1.94 (>120) | 3.68 ± 1.43 (>106) | 3.71 ± 1.30 (>105) | 4.04 ± 0.53 (>96) | 5.43 ± 1.08 (>72) | 0.18 ± 0.05 (>2 160) |
| 6a | 41.14 ± 3.15 | 2.68 ± 1.37 (15) | 3.43 ± 1.20 (12) | 2.88 ± 0.51 (14) | 3.15 ± 0.53 (13) | 4.06 ± 1.50 (10) | 0.22 ± 0.08 (187) |
| 7a | >286.25 | 0.50 ± 0.35 (>573) | 0.46 ± 0.07 (>622) | 0.55 ± 0.10 (>520) | 0.52 ± 0.09 (>550) | 0.62 ± 0.04 (>462) | 0.03 ± 0.01 (>9 542) |
| 8a | 18.44 ± 2.51 | 3.89 ± 2.14 (5) | 5.47 ± 0.23 (3) | 4.81 ± 1.10 (4) | 5.01 ± 1.18 (4) | 6.83 ± 2.66 (3) | 0.20 ± 0.07 (92) |
| 9a | 24.56 ± 15.79 | 1.29 ± 0.38 (19) | 1.50 ± 0.28 (16) | 1.31 ± 0.04 (19) | 1.24 ± 0.46 (20) | 1.74 ± 0.74 (14) | 0.17 ± 0.06 (144) |
| Nitrothienylazines | |||||||
| 1b | 10.37 ± 1.97 | 0.30 ± 0.10 (35) | 0.34 ± 0.01 (31) | 0.35 ± 0.02 (30) | 0.33 ± 0.09 (31) | 0.42 ± 0.02 (25) | 0.10 ± 0.04 (104) |
| 2b | 87.96 ± 66.83 | 0.46 ± 0.20 (191) | 0.57 ± 0.08 (154) | 0.59 ± 0.07 (149) | 0.57 ± 0.11 (154) | 0.67 ± 0.02 (131) | 0.06 ± 0.03 (1 466) |
| 3b | >340.45 | 0.84 ± 0.42 (>405) | 1.04 ± 0.23 (>327) | 0.95 ± 0.27 (>358) | 1.23 ± 0.16 (>277) | 1.34 ± 0.02 (>254) | 0.14 ± 0.06 (>2 432) |
| 4b | >295.70 | 0.82 ± 0.45 (>361) | 1.01 ± 0.25 (>293) | 0.94 ± 0.31 (>315) | 1.04 ± 0.35 (>384) | 1.83 ± 0.54 (>162) | 0.12 ± 0.03 (>2 464) |
| 5b | >365.88 | 2.09 ± 1.21 (>175) | 2.50 ± 0.81 (>146) | 2.07 ± 0.99 (>177) | 3.39 ± 0.44 (>108) | 5.17 ± 1.58 (>232) | 0.35 ± 0.10 (>1 045) |
| 6b | >345.65 | 1.05 ± 0.48 (>329) | 1.29 ± 0.20 (>268) | 1.30 ± 0.21 (>177) | 2.10 ± 0.41 (>165) | 2.65 ± 0.42 (>232) | 0.22 ± 0.04 (>1 571) |
| 7b | >273.67 | 4.88 ± 4.20 (>56) | 4.60 ± 0.73 (>59) | 4.10 ± 1.13 (>67) | 10.51 ± 3.76 (>26) | 12.30 ± 2.96 (>22) | 0.28 ± 0.08 (>977) |
| 8b | 9.26 ± 2.36 | 0.33 ± 0.12 (28) | 0.43 ± 0.14 (22) | 0.37 ± 0.05 (25) | 0.50 ± 0.09 (19) | 0.61 ± 0.02 (15) | 0.04 ± 0.01 (232) |
| 9b | >328.64 | 0.91 ± 0.51 (>361) | 0.97 ± 0.19 (>339) | 0.93 ± 0.23 (>353) | 1.01 ± 0.50 (>325) | 1.41 ± 0.20 (>233) | 0.06 ± 0.02 (>5 477) |
| Reference drugsd | |||||||
| eflornithine | - | 38.56 ± 9.88 | 36.66 ± 12.87 | 45.99 ± 17.07 | - | 57.21 ± 17.56 | 16.13 ± 2.93 |
| nifurtimox | - | 4.66 ± 19.70 | 4.58 ± 2.38 | 4.35 ± 1.59 | - | 2.62 ± 1.40 | 1.06 ± 0.22 |
| pentamidine | - | 0.041 ± 0.0023 | 0.014 ± 0.0031 | 0.029 ± 0.0062 | 0.0013 ± 0.0003 | 0.00097 ± 0.00019 | 0.33 ± 0.05 |
| suramin | - | 0.066 ± 0.0052 | 0.064 ± 0.0018 | 0.076 ± 0.011 | 0.038 ± 0.014 | 0.38 ± 0.058 | 7.17 ± 0.87 |
| diminazene aceturate | - | - | - | - | 0.011 ± 0.0029 | - | 0.109 ± 0.026 |
a
Half-maximal cytotoxic concentration (IC50, μM) represented as the mean ± standard deviation (SD), three biological replicates.
b
Half-maximal inhibitory concentration (IC50, μM) represented as the mean ± standard deviation (SD), four biological replicates.
c
Selectivity index (SI): CC50 of MDBK/IC50 of trypanosome.
e
MDBK: Madin–Darby bovine kidney cells; Tbb: Trypanosoma brucei brucei; Tbg: Trypanosoma brucei gambiense; Tbr: Trypanosoma brucei rhodesiense; Teq: Trypanosoma equiperdum; Tev: Trypanosoma evansi; Tc: Trypanosoma congolense; qualifies as trypanocidal hit if IC50 ≤ 10 μM and SI ≥ 10.53