Table 1.
Ability of Selected ML283 Analogues To Inhibit DENV Helicase-Catalyzed ATP Hydrolysis and RNA Unwinding
| ||||||
|---|---|---|---|---|---|---|
| compd (CID)a | R | DENV ATPase IC50b (μM) | DENV RNA- helicase IC50c (μM) | HCV ATPase IC50d (μM) | HCV DNA- helicase IC50e (μM) | HCV RNA-helicase IC50f (μM) |
| 1 (49849280) | H | 5.3 ± 1.2 | ndg | 69 ± 6 | 11 ± 1.5 | 8.5 ± 2 |
| 2 (49849300) | 4-NH2 | 2.8 ± 0.6 | 7.6 ± 1.6 | 58 ± 10 | 10 ± 2.4 | 7.0 ± 1* |
| 3 (49849294) | 4-F | 3.0 ± 0.4 | 6.6 ± 0.9 | 32 ± 7 | 5.2 ± 0.6 | 4.2 ± 2* |
| 4 (49849282) | 4-OCH3 | 3.0 ± 0.5 | nd | 115 ± 14 | 10 ± 2.6 | nd |
| 5 (49849290) | 4-CO2CH3 | 0.4 ± 0.1 | 7.9 ± 2.5 | >200 | 9.7 ± 4.6 | nd |
| 6 (49849302) | 4-Cl | 1.4 ± 0.2 | 5.6 ± 1.2 | 53 ± 4 | 3.4 ± 0.3 | 3.3 ± 1 |
| 7 (49849286) | 4-CH3 | 1.1 ± 0.2 | 4.3 ± 1.9 | 61 ± 1 | 3.3 ± 0.3 | 3.9 ± 1 |
| 8 (49849276) | 4-CF3 | 1.2 ± 0.2 | 5.2 ± 0.6 | 111 ± 60 | 1.8 ± 0.4 | 2.8 ± 2 |
| 9 (49849299) | 4-t-Bu | 4.0 ± 0.5 | 10 ± 3.4 | >200 | 8.2 ± 1 | 8.8 ± 3* |
| 10 (49849284) | 4-N(CH3)2 | 3.4 ± 0.3 | nd | >200 | 11 ± 6.7 | 8.6 ± 2 |
| 11 (50930740) | 4-Br | 1.1 ± 0.1 | 5.0 ± 1.2 | 21 ± 6 | 5.2 ± 4 | 3.8 ± 0.4* |
| 12 (46839370) | 4-NHFmoc | 1.3 ± 0.3 | 3.5 ± 1.7 | 39 ± 31 | 5.4 ± 1 | 2.8 ± 1 |
| 13 (50930730) | 3-Cl | 4.0 ± 0.8 | 5.1 ± 0.9 | 24 ± 5 | 2.6 ± 1 | 5.9 ± 2 |
| 14 (50930737) | 3,4-di-Cl | 2.7 ± 0.2 | 3.6 ± 0.9 | 53 ± 3 | 3.7 ± 1 | 3.9 ± 2* |
| 15 (50930748) | 2-CF3 | 5.4 ± 0.8 | nd | 71 ± 23 | 14 ± 1 | 22.8 ± 5 |
| 16 (50930755) | 3-CF3 | 9.7 ± 3.1 | nd | >200 | 20 ± 12 | 22.4 ± 8 |
| 17 (50930745) | 2-F,6-CF3 | 5.3 ± 6.8 | nd | 93 ± 16 | 17 ± 6 | 32.5 ± 7 |
| 18 (50930751) | 2-F,3-CF3 | 4.3 ± 0.3 | nd | 42 ± 14 | 9.2 ± 3 | 11.9 ± 4* |
| 19 (50930743) | 3-F,4-CF3 | 3.5 ± 1.1 | nd | 55 ± 42 | 17 ± 7 | 5.4 ± 2 |
| 20 (50930749) | 3,5-di-CF3 | 63 ± 20 | 7.7 ± 1.8 | >200 | 22 ± 4 | 14.2 ± 2* |
| 21 (50930741) | 2-F,5-CF3 | 3.8 ± 0.2 | 5.4 ± 1.3 | 16 ± 2 | 6.4 ± 2 | 7.5 ± 2 |
| 22 (50930733) | 3-F,6-CF3 | 7.2 ± 0.8 | nd | 65 ± 10 | 19 ± 15 | nd |
| 23 (50930732) | 3-F,5-CF3 | 11 ± 5.7 | nd | >200 | 28 ± 7 | 9.8 ± 3 |
a
PubChem40 compound identification number (CID).
b
Half-maximal inhibitory concentration observed in assays monitoring DENV NS3h-catalyzed ATP hydrolysis.
c
Half-maximal inhibitory concentration observed in assays monitoring DENV NS3h RNA unwinding.
d
Half-maximal inhibitory concentration observed in assays monitoring HCV NS3h-catalyzed ATP hydrolysis.
e
Half-maximal inhibitory concentration in assays monitoring HCV NS3h DNA unwinding. Data from Li et al.36
f
Half-maximal inhibitory concentration in assays monitoring HCV NS3h RNA unwinding. Values marked with asterisks (*) were published previously in Ndjomou et al.12
g
nd, not determined.