Table 1.
Inhibition of Giardia duodenalis by Library 1 Robenidine analogues possessing mono‐halogenated aromatic rings (4–13).[a]
|
|
|
Antigiardial activity |
|
|
|
|
|---|---|---|---|---|---|---|
|
Compound |
R |
MIC [μM] (24 h) |
IC50 [μM] (24 h) |
Antibacterial activity (Y/N)[b] |
Toxicity (Y/N) (% growth control)[c] |
Selectivity ratio[d] |
|
Metronidazole |
– |
8.3 |
3.8 |
N |
N |
>6.6 |
|
Robenidine 4 |
4‐Cl |
2.8 |
0.9 |
Y |
Y (40.7±22.6) |
>27.8 |
|
5 |
H |
– |
– |
N |
– |
– |
|
6 |
4‐Br |
8.3 |
1.7 |
N |
N (97.1±1.6) |
>14.7 |
|
7 |
4‐F |
12.5 |
6.52 |
Y |
– |
– |
|
8 |
3‐Cl |
6.25 |
3.5 |
Y |
– |
– |
|
9 |
3‐Br |
25 |
2.9 |
Y |
– |
– |
|
10 |
3‐F |
>25 |
>25 |
Y |
– |
– |
|
11 |
2‐Br |
25 |
0.8 |
N |
Y (79.1±2.3) |
>31.3 |
|
12 |
2‐Cl |
25 |
12.37 |
N |
– |
– |
|
13 |
2‐F |
>25 |
>25 |
N |
N[e] (93.9±1.9) |
– |
[a] Toxicity (CaCo‐2 and Vero cells) and antimicrobial assays performed at 25 μM; MIC: minimum inhibitory concentration; ‘–’ not tested, as inhibitory activity at 25 μM<50 %. [b] MSRA and VRE. [c] Percent CaCo‐2 cell growth (25 μM); compounds are indicated as toxic if >20 % cells are affected. [d] Higher ratios indicate a more selective compound. [e] Toxicity assessed with Vero cells, not CaCo‐2 cells.