Table 2 In vitro antileishmanial activity and CYP inhibition of antifungal azoles and non-azole compounds
Compound | EC50 or IC50 (μM) | SIc | ||
|---|---|---|---|---|
EC50 (L. donovani)a | IC50 (LdCYP51)b | IC50 (LdCYP5122A1)b | ||
Imidazole | ||||
Bifonazole | 12 ± 1 | 0.057 ± 0.008 | 0.33 ± 0.07 | 5.7 |
Butoconazole | 1.9 ± 0.4 | 0.073 ± 0.008 | 0.32 ± 0.07 | 4.4 |
Clotrimazole | 5.0 ± 0.1 | 0.068 ± 0.004 | 0.26 ± 0.08 | 3.8 |
Econazole | 9.4 ± 0.3 | 0.046 ± 0.004 | 0.47 ± 0.13 | 10 |
Fenticonazole | 5.6 ± 0.3 | 0.081 ± 0.002 | 0.65 ± 0.08 | 8.0 |
Isoconazole | 6.2 ± 0.5 | 0.049 ± 0.003 | 0.43 ± 0.04 | 8.8 |
Ketoconazole | 22 ± 6 | 0.048 ± 0.007 | 0.42 ± 0.05 | 8.7 |
Miconazole | 7.6 ± 0.7 | 0.057 ± 0.003 | 1.1 ± 0.2 | 19 |
Oxiconazole | 3.9 ± 0.4 | 0.032 ± 0.002 | 0.62 ± 0.02 | 20 |
Sertaconazole | 7.1 ± 0.5 | 0.064 ± 0.007 | 1.1 ± 0.2 | 17 |
Sulconazole | 7.4 ± 0.6 | 0.064 ± 0.003 | 0.38 ± 0.06 | 5.9 |
Tioconazole | 9.5 ± 0.6 | 0.054 ± 0.008 | 1.1 ± 0.2 | 20 |
Triazole | ||||
Efinaconazole | 15 ± 1 | 0.068 ± 0.002 | 6.2 ± 1.7 | 92 |
Fluconazole | >100d | 0.96 ± 0.05 | >100 | >105 |
Isavuconazole | 12 ± 0 | 0.043 ± 0.007 | 2.6 ± 0.7 | 60 |
Itraconazole | 6.0 ± 1.1 | 0.049 ± 0.009 | 2.1 ± 0.4 | 43 |
Posaconazole | 2.8d | 0.059 ± 0.003 | 1.5 ± 0.3 | 25 |
Ravuconazole | 12 ± 2 | 0.049 ± 0.008 | 12 ± 4 | 248 |
Terconazole | 13 ± 1 | 0.083 ± 0.009 | 12 ± 3 | 140 |
Voriconazole | >100 | 0.085 ± 0.017 | >100 | >1176 |
Non azole compounds | ||||
Miltefosine | 2.7e | 12 ± 1 | 43 ± 1 | 3.5 |
Pentamidine | 14 ± 1 | No inhibition at 100 μM | No inhibition at 100 μM | NA |
Paromomycin | >50e | No inhibition at 100 μM | No inhibition at 100 μM | NA |
Amphotericin B | 0.14 ± 0.01 | <25% inhibition at 10 μM | <25% inhibition at 10 μM | NA |
DB766 | 0.036f | <30% inhibition at 30 μM | 1.0 ± 0.1 | <0.035 |
