Table 2.
In vitro antituberculosis activity reported in minimum inhibitory concentration (MIC, µM) (MABA and LORA), MABA MIC of selected compounds against isogenic monodrug-resistant M. tb., rRMP and rINH, spectrum of activity and selectivity index of designed chalcones.
| Code | Compounds | Minimum Inhibitory Concentration (µM) | SI | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|||||||||||||
|
MABA | LORA | rRMP | rINH | C. albicans | E. coli | S. aureus | M. smegmatis | |||||
| R1 | R2 | R3 | R4 | ||||||||||
| 3 | H | H | Br |
|
2.50 | 6.76 | 0.76 | 0.58 | 4.93 | >10 | 0.36 | 7.12 | ND |
| 4 | H | H |
|
|
0.81 | 9.85 | 0.55 | 0.11 | >10 | >10 | 1.19 | >10 | 123 |
| 5 | H | H |
|
|
3.42 | 10.91 | 0.07 | <0.03 | >10 | >10 | >10 | >10 | ND |
| 6 | H | H |
|
|
1.05 | 6.94 | 1.19 | 1.44 | >10 | 3.18 | 0.34 | >10 | 94 |
| 7 | H | H | -C(CH3)3 |
|
0.35 | >10 | 0.29 | 0.22 | >10 | >10 | >10 | >10 | 284 |
| 8 | H | H |
|
|
0.81 | 3.33 | 1.12 | 1.23 | >10 | >10 | >10 | >10 | 122 |
| 9 | H | H |
|
|
0.27 | 9.67 | 0.76 | 0.19 | >10 | >10 | >10 | >10 | 359 |
| 10 | H | H |
|
|
3.91 | 3.18 | 3.45 | 0.29 | >10 | >10 | >10 | >10 | 25 |
| 11 | -CH3 | H | H |
|
0.57 | 4.59 | 1.08 | 1.07 | 6.36 | >10 | 1.09 | 9.50 | 41 |
| 12 | H | H | -(CH2)3CH3 |
|
1.31 | 4.21 | 4.70 | 2.23 | >10 | >10 | 2.23 | >10 | 57 |
| 13 | H | H | -I |
|
0.60 | 4.12 | 1.18 | 1.08 | >10 | >10 | >10 | 4.62 | 166 |
| 14 | H | -CH3 | H |
|
1.27 | 4.75 | 3.78 | 1.93 | >10 | >10 | 2.23 | >10 | 43 |
| 15 | H | H |
|
|
>10 | 4.30 | - | - | >10 | >10 | >10 | >10 | ND |
| 16 | H | -Br | H |
|
1.32 | 5.65 | 1.88 | 1.12 | >10 | >10 | 1.68 | 4.84 | 52 |
| 17 | H | H | -SCH3 |
|
0.66 | 5.07 | 0.24 | 0.80 | >10 | >10 | 0.58 | 4.81 | 61 |
| 18 | H | H |
|
|
0.19 | 1.73 | 0.60 | 0.30 | >10 | >10 | 0.28 | 4.39 | 225 |
| 19 | H | H | -C(CH3)3 |
|
0.22 | 4.18 | 0.14 | 0.15 | >10 | >10 | >10 | >10 | 454 |
| 20 | H | H | -(CH2)3CH3 |
|
0.54 | 5.56 | 0.48 | 0.31 | >10 | >10 | >10 | >10 | 81 |
| 21 | H | H |
|
|
>10 | 5.75 | - | - | >10 | >10 | >10 | >10 | ND |
| 22 | H | H |
|
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 23 | H | H | -SCH3 |
|
0.45 | 5.96 | 0.14 | 0.22 | >10 | >10 | >10 | >10 | 222 |
| 24 | H | H | -CH3 |
|
1.87 | 2.05 | 1.21 | 0.96 | >10 | >10 | >10 | >10 | ND |
| 25 | H | H |
|
|
9.29 | 9.75 | 8.89 | 9.03 | >10 | >10 | >10 | >10 | ND |
| 26 | H | H |
|
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 27 | H | H |
|
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 28 | H | H |
|
|
>10 | >10 | - | - | >10 | >10 | 1.18 | >10 | ND |
| 29 | H | H | -SCH3 |
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 30 | H | -I | H |
|
4.90 | >10 | 8.31 | 7.75 | >10 | >10 | >10 | >10 | 20 |
| 31 | H | H |
|
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 32 | H | -Br | H |
|
8.54 | 8.20 | 9.28 | 4.94 | >10 | >10 | >10 | >10 | 11 |
| 33 | H | H | -C(CH3)3 |
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 34 | H | H |
|
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| 35 | H | H | -C(CH3)3 |
|
>10 | >10 | - | - | >10 | >10 | >10 | >10 | ND |
| RMP | 0.05 | 0.19 | >1 | - | - | - | - | >10 | 2000 | ||||
| INH | 0.41 | >256 | - | >5 | - | - | - | >10 | |||||
| Amph. B | - | - | - | - | <0.004 | - | - | - | |||||
| Amp | - | - | - | - | - | 1.18 | 0.25 | - | |||||
MABA: Microplate Alamar Blue Assay; LORA: Low Oxygen Recovery Assay; rRMP: monoresistant to rifampin; rINH: monoresistant to isoniazid. SI: Selectivity Index (Vero Cell IC50/MABA MIC). RMP: rifampin, INH: isoniazid, Amph. B: amphotericin B, Amp.: ampicillin