Table 1.
In vitro antimycobacterial activity against Mtb H37Ra, Mycobacterium aurum and M. smegmatis (MIC in µg/mL), cytotoxicity (IC50), selectivity index (SI), and calculated lipophilicity (logP) of prepared compounds.
| No. | R1 | R2 | Mtb H37Ra |
Mycobacterium
aurum |
Mycobacterium
smegmatis |
HepG2 IC50 (µM) | SI a | logP |
|---|---|---|---|---|---|---|---|---|
| 1 | 3-CF3 | - | 7.81 | ≥500 | ≥500 | 123.8 | 4.78 | 2.41 |
| 1a | 3-CF3 | Propyl | 6.25 | ≥500 | ≥500 | >25 | >1.3 | 2.55 |
| 1b | 3-CF3 | Butyl | 3.13 | 6.25 | 3.13 | 125.6 | 13.6 | 2.96 |
| 1c | 3-CF3 | Pentyl | 3.13 | 3.13 | 1.56 | 18.9 | 2.13 | 3.38 |
| 1d | 3-CF3 | Hexyl | ≥500 | 25 | ≥500 | >25 | n.a. | 3.80 |
| 1e | 3-CF3 | Heptyl | ≥500 | 62.5 | ≥500 | 222.9 | n.a. | 4.22 |
| 1f | 3-CF3 | Octyl | ≥500 | ≥500 | ≥500 | 66.2 | n.a. | 4.63 |
| 2 | 3-OH | - | 31.25 | ≥500 | ≥500 | >500 | >3.99 | 1.10 |
| 2a | 3-OH | Propyl | 7.81 | ≥500 | ≥500 | >100 | >3.5 | 1.24 |
| 2b | 3-OH | Butyl | 7.81 | ≥500 | ≥500 | >25 | >0.92 | 1.65 |
| 2c | 3-OH | Pentyl | ≥500 | ≥500 | ≥500 | >10 | n.a. | 2.07 |
| 2d | 3-OH | Hexyl | ≥500 | ≥500 | ≥500 | >10 | n.a. | 2.49 |
| 2e | 3-OH | Heptyl | ≥500 | ≥500 | 250 | >10 | n.a. | 2.91 |
| 2f | 3-OH | Octyl | ≥500 | ≥500 | 250 | >50 | n.a. | 3.32 |
| 3 | 4-OH | - | 62.50 | ≥250 | ≥250 | 350.2 | 1.40 | 1.10 |
| 3a | 4-OH | Propyl | 15.63 | ≥500 | ≥500 | 410.5 | 7.18 | 1.24 |
| 3b | 4-OH | Butyl | 31.25 | ≥500 | ≥500 | 377.9 | 3.46 | 1.65 |
| 3c | 4-OH | Pentyl | 3.91 | ≥500 | 31.25 | >500 | >38.4 | 2.07 |
| 3d | 4-OH | Hexyl | 3.91 | ≥500 | 250 | 58.6 | 4.71 | 2.49 |
| 3e | 4-OH | Heptyl | 3.91 | ≥500 | 31.25 | 44.8 | 3.76 | 2.91 |
| 3f | 4-OH | Octyl | 3.13 | ≥250 | ≥250 | 60.2 | 6.6 | 3.32 |
| 4 | 4-CH3 | - | ≥500 | ≥500 | ≥500 | >50 | n.a. | 1.98 |
| 4a | 4-CH3 | Propyl | 15.63 | ≥500 | 31.25 | >100 | >1.73 | 2.11 |
| 4b | 4-CH3 | Butyl | ≥ 250 | ≥250 | ≥250 | >50 | n.a. | 2.53 |
| 4c | 4-CH3 | Pentyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 2.95 |
| 4d | 4-CH3 | Hexyl | 1.56 | ≥500 | ≥500 | >50 | >10.01 | 3.36 |
| 4e | 4-CH3 | Heptyl | 0.78 | ≥500 | ≥500 | >50 | >20.91 | 3.78 |
| 4f | 4-CH3 | Octyl | ≥250 | ≥250 | ≥250 | >25 | n.a. | 4.20 |
| 5 | 4-C2H5 | - | 250 | ≥500 | ≥500 | >50 | n.a. | 3.29 |
| 5a | 4-C2H5 | Propyl | 7.81 | ≥500 | 7.81 | 494.6 | 18.01 | 2.53 |
| 5b | 4-C2H5 | Butyl | ≥500 | ≥500 | ≥500 | >50 | n.a. | 2.95 |
| 5c | 4-C2H5 | Pentyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 3.36 |
| 5d | 4-C2H5 | Hexyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 3.78 |
| 5e | 4-C2H5 | Heptyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 4.20 |
| 5f | 4-C2H5 | Octyl | ≥250 | ≥250 | ≥250 | >10 | n.a. | 4.62 |
| 6 | 4-Cl-2-OH | - | ≥500 | ≥500 | ≥500 | >250 | n.a. | 1.66 |
| 6a | 4-Cl-2-OH | Propyl | ≥500 | ≥500 | 3.91 | n.a. | n.a. | 1.79 |
| 6b | 4-Cl-2-OH | Butyl | ≥500 | ≥500 | 3.91 | >50 | n.a. | 2.21 |
| 6c | 4-Cl-2-OH | Pentyl | ≥500 | ≥500 | 3.91 | 81.1 | n.a. | 2.63 |
| 6d | 4-Cl-2-OH | Hexyl | 3.13 | ≥500 | 3.91 | >50 | >5.27 | 3.05 |
| 6e | 4-Cl-2-OH | Heptyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 3.46 |
| 6f | 4-Cl-2-OH | Octyl | ≥500 | ≥500 | 7.81 | >50 | n.a. | 3.88 |
| 7 | 5-Cl-2-OH | - | 15.63 | 31.25 | 15.63 | 151.2 | 2.75 | 1.66 |
| 7a | 5-Cl-2-OH | Propyl | ≥500 | 250 | <3.91 | >25 | n.a. | 1.79 |
| 7b | 5-Cl-2-OH | Butyl | ≥500 | ≥500 | 3.91 | >25 | n.a. | 2.21 |
| 7c | 5-Cl-2-OH | Pentyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 2.63 |
| 7d | 5-Cl-2-OH | Hexyl | ≥500 | ≥500 | ≥500 | >25 | n.a. | 3.05 |
| 7e | 5-Cl-2-OH | Heptyl | ≥500 | ≥500 | 31.25 | >10 | >0.32 | 3.46 |
| 7f | 5-Cl-2-OH | Octyl | ≥500 | ≥500 | 250 | >50 | n.a. | 3.88 |
| INH | 0.125–0.250 | 3.91–7.81 | 7.81–15.63 | |||||
| RIF | 0.0039–0.0078 | 0.39–0.78 | 6.25–12.5 | |||||
| CPX | 0.125–0.25 | 0.0156–0.0313 | 0.0625–0.125 | |||||
a SI—Selectivity index, values calculated from MIC against Mtb H37Ra as IC50/MIC (in µM); n.a.—not available; INH—isoniazid; RIF—rifampicin; CPX—ciprofloxacin. In the column HepG2 IC50 (µM), symbol “>” means that measurement at higher concentration was not reproducible due to the precipitation of the tested compound in the cell culture medium.