Table 1.
Reported (1-benzyl-4-triazolyl)-indole-2-carboxamides and related compounds with their overall yields, ClogP values, and IC50 indices against T. gondii and C. parvum as well as cytotoxicity in mammalian HCT-8 and HFF cell lines.
| Compound |
Yielda | ClogPb | Parasite IC50 (μM) |
Host cell IC50 (μM) |
SIg |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Code | No. |
T. gondii |
C. parvum |
HCT-8 | HFF | T. gondii | C. parvum | ||||
| 0h p.ic | 2h p.id | 0h p.i | 2h p.i | ||||||||
| JS-2-15 | 5a | 68 | 3.00 | NAe | NA | NA | NA | 109.0 | NDf | ||
| JS-2-22 | 5b | 58 | 4.14 | NA | NA | 12.30 | 12.54 | 101.4 | ND | 8.24 | |
| JS-2-18 | 6a | 51 | 3.65 | NA | NA | NA | NA | 205.0 | ND | ||
| JS-2-25 | 6b | 55 | 4.36 | NA | NA | NA | NA | 106.7 | ND | ||
| JS-2-26 | 6c | 54 | 4.36 | NA | NA | NA | NA | ND | ND | ||
| JS-2-32 | 6d | 58 | 4.36 | NA | NA | NA | NA | ND | ND | ||
| JS-2-43 | 6e | 79 | 4.95 | NA | NA | NA | NA | 174.4 | ND | ||
| JS-2-27 | 7a | 89 | 4.79 | NA | NA | 9.37 | 10.73 | 253.8 | ND | 27.09 | |
| JS-2-28 | 7b | 67 | 5.50 | 11.63 | 19.23 | 8.32 | 8.59 | 233.4 | 209.4 | 20.07 | 28.05 |
| JS-2-30 | 7c | 76 | 5.50 | 5.43 | 6.32 | 5.05 | 5.86 | 192.70 | 268.0 | 35.49 | 38.16 |
| JS-2-33 | 7d | 65 | 5.50 | NA | NA | NA | NA | ND | ND | ||
| JS-2-44 | 7e | 51 | 6.09 | 2.95 (10.55)h | 3.24 | 7.63 | 9.12 | 209.7 | 209.1 | 71.08 | 27.48 |
| JS-2-19 | 9a | 36 | 4.54 | 8.51 | 10.60 | NA | NA | ND | 107.7 | 12.66 | |
| JS-2-31 | 9b | 31 | 5.68 | 7.88 | 12.08 | NA | NA | ND | 135.1 | 17.15 | |
| JS-2-40 | 11a | 24 | 4.23 | NA | NA | NA | NA | 134.8 | ND | ||
| JS-2-41 | 11b | 18 | 4.36 | 1.94 (1.50)h | 2.15 | NA | NA | ND | 167.8 | 86.50 | |
| ATQi | 0.084 | 0.087 | |||||||||
| PMOj | 219.5 | 226.8 | |||||||||
a
Yield reported after purification by flash chromatography on silica.
b
Calculated with ChemDraw Professional 15.1.
c
Test compound added immediately post-infection.
d
Test compound added 2 h post-infection.
e
NA = not active in the primary compound screening.
f
ND = not done.
g
SI = selectivity index = IC50 HCT-8 (or HFF)/IC50 parasite (at 0 h p.i.).
h
Against T. gondii Type II (ME49) in HFF cells.
i
ATQ = standard drug atovaquone.
j
PMO = standard drug paromomycin.