Table 1. Host cell toxicity and efficacy of compounds against L. donovani intracellular amastigotes, promastigotes and axenic amastigotes.
Compounds | GI50 THP-1 (µM) | GI50 Intracellular amastigote (µM) | GI50 Promastigote (µM) | GI50 Axenic amastigote (µM) | Selectivitya | Specificityb |
Naloxonazine | 33.8 | 3.49 | >50 | >50 | 9.68 | 14.32 |
Metergoline | 37.14 | 0.78 | 15.08 | >50 | 47.22 | 19.17 |
R(-)-Apomorphine | >16.5 | 2.7 | 38.15 | 5.20 | 6.1 | 14.12 |
Clotrimazole | >16.5 | 1.08 | 12.92 | 4.56 | 15.32 | 11.92 |
Cetylpyridinium chloride | 9.16 | 0.41 | 3.30 | 0.92 | 22.34 | 8.05 |
Aminacrine | 12.97 | 1.9 | 8.96 | >16.5 | 6.82 | 4.71 |
4,4′-Diethylaminoethoxyhexestrol | 6.11 | 1.4 | 5 | 10.93 | 4.36 | 3.57 |
Hexachlorophene | 16.5 | 4.54 | 15.88 | 14.76 | 3.62 | 3.49 |
Loperamide Hydrochloride | >16.5 | 5.4 | 17.3 | >50 | 3.02 | 3.15 |
Tamsulosin | 27.97 | 6.3 | 20 | >50 | 4.43 | 3.17 |
Salinomycin | 16.09 | 0.92 | 2.71 | 0.06 | 17.30 | 2.92 |
Cycloheximide | 21 | 1.15 | 2.95 | 0.39 | 18.13 | 2.55 |
Prazocin Hydrochloride | 23.32 | 6.73 | 16.74 | >50 | 3.46 | 2.48 |
Carvedilol | 37.5 | 6.16 | 12.41 | >16.5 | 6.07 | 2.01 |
Brilliant green | 1.64 | 6 | 0.10 | 0.03 | 15.88 | 0.02 |
Antimycin A | >50 | 2.15 | 0.1 | 0.01 | 500 | 0.05 |
BAY 11–7085 | >50 | >16,5 | 1.54 | 0.42 | 32.46 | 0.06 |
Haloprogin | 20 | 6 | 1.05 | 0.56 | 19.04 | 0.17 |
Pentamidine Isethionate | >50 | 9.55 | 1.69 | 1.64 | 29.49 | 0.17 |
Zinc Dibutyldithiocarbamate | >50 | >50 | 8.48 | >50 | 5.89 | 0.17 |
Amlodipine | >16.5 | 9.78 | 3.11 | 27 | 5.34 | 0.31 |
Nisoldipine | >16,5 | 32.17 | 9.85 | 13.86 | 1.67 | 0.30 |
Parthenolide | >16.5 | >50 | 15.54 | 4.35 | 1.06 | 0.31 |
Pyrithione zinc | 1.043 | ND | 0.07 | 0.01 | 14.9 | ND |
Thimerosal | 12.81 | ND | 0.49 | 1.50 | 26.18 | ND |
Gramicidin | 8.38 | ND | 0.68 | 5.76 | 12.19 | ND |
Digitonin | 13.46 | ND | 4.376 | 13.81 | 3.075 | ND |
Emetine | 1.28 | 0.082 | 0.03 | 1.62 | 15.58 | 0.42 |
Amphotericin B | >50 | 1.12 | 1.61 | 5.42 | 44.52 | 1.43 |
Chlorhexidine | >16,5 | 1.79 | 2.81 | 4.78 | 9.27 | 1.56 |
Oxiconazole | >16,5 | 6.6 | 2.65 | 0.53 | 2.51 | 0.40 |
Bazedoxifene | >16,5 | 4.8 | 6.52 | >16.5 | 3.45 | 1.35 |
chlorquinaldol | 39.3 | 5.5 | 6.3 | 1.72 | 7.14 | 1.14 |
Doxazocin | >16,5 | 5 | 8.45 | >16.5 | 3.32 | 1.69 |
Aclacynomycine a1 | 29.1 | 5.81 | 9.15 | >16.5 | 5 | 1.57 |
Mebeverine | >50 | 8.5 | 6.91 | 2.36 | 5.88 | 0.81 |
Miconazole | >16,5 | 15.44 | 7.48 | 4.73 | 1.07 | 0.48 |
Terfenadine | 39.03 | 14.4 | 11.92 | 0.61 | 2.71 | 0.82 |
Tamoxifen Citrate | >16.5 | 20.79 | 10.22 | >50 | 1.61 | 0.49 |
Auranofin | 20.89 | 21.76 | 11.11 | >50 | 1.88 | 0.51 |
Benzetonium chloride | 40.18 | 10 | 11.34 | 10.7 | 3.54 | 1.13 |
Ciclopirox | 42 | 22 | 15.25 | >50 | 1.90 | 0.69 |
Sporidesmin A | 0.02 | ND | 1.18 | 1.66 | 0.02 | ND |
Harringtonin | 0.10 | 4.89 | 16.61 | 10.6 | 0.02 | 3.39 |
3,3′,4′,5-tetrachlorosalicylanilide | 0.32 | ND | 1.45 | 1.38 | 0.22 | ND |
Thiram | 1.58 | 10.4 | 4.62 | 5.42 | 0.34 | 0.44 |
Idarubicin | 1.89 | ND | 4.65 | 1.78 | 0.40 | ND |
Cerivastatin | 7.15 | >50 | 10.8 | 0.02 | 0.66 | 0.22 |
aSelectivity is the ratio between parasite GI50 and THP-1 GI50.
bSpecificity is the ratio between promastigote GI50 and intracellular amastigote GI50. Specificity value >2 was the cut-off chosen to define a compound as more active against the intracellular amastigote stage; while a specificity value <0.4 indicated a compound more active against promastigotes; compounds with specificity values between 0.4 and 2 were considered active against both stages.