Table 4.
Inhibition of Giardia duodenalis metabolism by Library 4 Robenidine analogues possessing di‐, tri‐ and poly‐substituted aromatic rings (34–47).[a]
|
|
|
Antigiardial activity |
|
|
|
|
|---|---|---|---|---|---|---|
|
Compound |
R |
MLC [μM] (24 h) |
IC50 [μM] (5 h) |
Antibacterial activity (Y/N)[b] |
Toxicity (Y/N) (% growth control)[c] |
Selectivity ratio[d] |
|
34 |
2,4‐Cl |
3.13 |
2.49 |
N |
Y[e] (55.8±4.3) |
>10.0 |
|
35 |
3,5‐Cl |
25 |
11.6 |
N |
– |
– |
|
36 |
2,6‐Cl |
– |
– |
N |
– |
– |
|
37 |
2,5‐F |
– |
– |
N |
– |
– |
|
38 |
3,4‐F |
8.3 |
1.2 |
Y |
– |
– |
|
39 |
2,3,4,5,6‐F |
– |
– |
N |
– |
– |
|
40 |
2‐NHCOCH3, 4‐Cl |
25 |
0.8 |
N |
Y (83.1±4.4) |
>31.3 |
|
41 |
2‐Br, 4,5‐OCH3 |
2.8 |
0.2 |
N |
N |
>125 |
|
42 |
3‐Br, 4,5‐OCH3 |
3.13 |
2.7 |
N |
Y[e] |
>9.3 |
|
43 |
2‐OH, 4‐N(CH3)2 |
– |
– |
Y |
– |
– |
|
44 |
3,4‐OCH3 |
>25 |
24.9 |
N |
– |
– |
|
45 |
3‐NO2, 4‐OH |
– |
– |
N |
– |
– |
|
46 |
3‐OH, 4‐OCH3 |
– |
– |
N |
– |
– |
|
47 |
3‐OCH3, 4‐OH |
>25 |
>25 |
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 >10 % cells are affected. [d] Higher ratios indicate a more selective compound. [e] Toxicity assessed with Vero cells, not CaCo‐2 cells.