Table 3.
Inhibition Giardia duodenalis metabolism by Library 3 Robenidine analogues possessing heteroatom‐substituted aromatic rings (24–33).[a]
|
|
|
Antigiardial activity |
|
|
|
|
|---|---|---|---|---|---|---|
|
Compound |
R |
MLC [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 |
|
24 |
4‐OCH3 |
12.5 |
5.99 |
N |
Y[e] |
>4.2 |
|
25 |
3‐OCH3 |
>25 |
>25 |
Y |
– |
– |
|
26 |
2‐OCH3 |
>25 |
>25 |
Y |
– |
– |
|
27 |
4‐OH |
>25 |
>25 |
Y |
– |
– |
|
28 |
3‐OH |
>25 |
>25 |
Y |
– |
– |
|
29 |
2‐OH |
>25 |
>25 |
Y |
– |
– |
|
30 |
4‐OCF3 |
2.8 |
0.2 |
Y |
– |
– |
|
31 |
4‐SCH3 |
8.3 |
0.9 |
Y |
– |
– |
|
32 |
4‐SCF3 |
2.8 |
0.2 |
Y |
– |
– |
|
33 |
4‐N(CH3)2 |
25 |
1.1 |
Y |
– |
– |
[a] Toxicity (CaCo‐2 and Vero cells) and antimicrobial assays performed at 25 μM; MLC: minimum lethal 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.