Skip to main content
. 2018 Aug 22;157:1017–1030. doi: 10.1016/j.ejmech.2018.08.058

Table 1.

Activity in influenza virus-infected MDCKa cells.

Compound*
 Antiviral EC50b
 Cytotoxicityc
A/H1N1
 A/H1N1pdm
 A/H3N2
 Influenza B
CPE
 MTS
 CPE
 MTS
 CPE
 MTS
 CPE
 MTS
 CC50
 MCC
(μM)
1a 0.80 1.2 1.4 <0.80 1.8 1.2 >100# >100# 11 20
Series 1: Maleimide derivatives
12 (2x C3) >100 >100 1.8 2.0 >100 >100 >100 7.2 18 20
13 (2x C4) >100 >100 2.9 2.6 >100 >100 >100 >100 8.6 4
14 (2x C6) >100 >100 >100 >100 >100 >100 >100 >100 9.8 4
15 (2x C8) >100 >100 2.1 1.9 >100 >100 >100# >100# 11 20
16 (2x C12) >100 >100 >100 >100 >100 >100 >100 >100 ≤1.1 ≤4.0
17 (C3, C12) >100 10 5.1 8.2 7.3 6.8 8.9 7.3 29 ≥20
18 (2 x Galp) >100 9.1 2.1 2.2 2.3 1.7 >100 4.2 26 20



Series 2: Maleimide derivatives with a triazole linker
26 (2x C3) >100 >100 >100 >100 >100 >100 >100# >100# 22 20
27 (2x C4) 2.1 3.2 9.8 7.4 >100 4.9 2.5 3.5 28 20
28 (2x C6) 3.1 >100 4.0 2.9 1.9 1.9 2.3 2.7 12 ≥4
29 (2x C8) 9.2 12 4.4 3.4 8.9 6.3 6.7 7.2 49 73
30 (2x C12) >100 >100 >100 >100 >100 >100 >100# >100# 75 100
31 (2 x Galp) >100 >100 >100 >100 >100 >100 >100# >100# 18 20



Series 3: Maleimide derivatives with a triazolyl TEG linker
40 (2x C3) >100 >100 >100 7.8 6.2 ≤7.8 >100# >100# 38 20
41 (2x C4) 4.8 5.8 9.5 8.6 5.3 6.0 5.5 4.9 >100 100
42 (2x C6) 2.0 3.5 2.7 6.0 2.0 2.9 1.8 3.6 65 20
43 (2x C8) 1.3 2.0 ≤1.4 ≤0.80 0.92 ≤0.80 >20# >20# 19 ≥4.0
44 (2x C12) >100 13 >100 2.8 >100 2.4 >100 >100 79 20
45 (2x TEG) >100 >100 >100 >100 >100 >100 >100 >100 3.0 4.0
46 (2 x Galp) >100 >100 >100 >100 >100 23 >100 42 ≥32 >100



Series 4: Triazole derivatives [21]
2a (C16) 1.6 1.8 1.8 1.8 ≤8.9 ≤1.6 1.8# 1.3# 7.6 ≥4.0
2b (C12) >100 >100 >100 >100 >100 >100 >100# >100# 2.3 9.3
2c (C10) >100 >100 >100 >100 >100 >100 >100# >100# 3.7 4
2d (C8) >100 2.2 1.8 1.9 2.1 1.5 1.8# 1.9# 13 ≥4.0
2e (C6) >100 >100 >100 >100 15 13 17# 11# 53 ≥20
2f (Ph) >100 >100 >100 >100 11 11 >100# >100# 41 ≥20
2g (α-Np) 11 11 11 4.4 15 8 15# 6.6# 47 20
2h (Galp) 52 47 45 43 39 24 39# 29# >100 ≥100
2i (lactose) >100 >100 8.9 7.3 8.9 20 6.6# 4.0# >100 ≥20
2j (calixarene) >100 43 8.9 6.7 >100 5.2 >100# 5.7# ≥58 ≥20



Series 5: Triazole derivatives with a TEG linker and single alkyl chains
60 (C4) >100 51 >100 47 >100 31 >100 28 >100 100
61 (C6) >100 >100 >100 >100 >100 >100 >100 >100 51 100
62 (C8) >100 >100 >100 >100 >100 >100 >100 >100 19 20
63 (C10) 1.6 1.5 1.8 1.8 1.6 1.3 >100 <0.80 ≥82 ≥20



Series 6: Sulfonamide derivatives
72 (toluyl) 9 11 30 32 41 19 11 12 >100 100
73 (Ph) 16 27 46 52 25 23 51 21 >100 100
74 (PhNHAc) >100 >100 >100 >100 >100 >100 >100 47 60 100
75 (biphenyl) 1.8 1.7 2.0 2.0 1.5 1.6 1.8 2.4 15 11
76 (dansyl) 4.9 7.0 6.3 5.9 8.3 2.3 6.7 5.3 52 20
77 (C6) 8.6 9.6 8.9 9.1 8.3 8.9 8.9 10.3 54 100
78 (C8) 1.9 2.5 >100 >100 2.0 2.4 4.0 >100 14 20
79 (C12) 0.4 0.8 >100 1.6 <0.8 <0.8 <0.8 <0.8 4.5 4.0



Zanamivir 0.041 0.19 1.9 30 20 3.2 0.0079 0.0062 >100 >100
Ribavirin 8.4 9.1 10 8.5 13 5.9 2.3 2.2 >100 >100
Amantadine >500 >500 >500 >500 11 1.9 >500 >500 >500 >500
Rimantadine >500 >500 >500 >500 0.20 0.17 >500 >500 >500 >500

*Lipophilic substituents are specified in brackets.

aMDCK, Madin-Darby canine kidney cells.

bAntiviral activity expressed as the EC50, i.e. the compound concentration producing 50% inhibition of virus replication, as estimated by microscopic scoring of the cytopathic effect (CPE) or by measuring cell viability in the formazan-based MTS assay. Influenza strains: A/PR/8/34 (A/H1N1); A/Virginia/ATCC3/2009 (A/H1N1pdm); A/HK/7/87 (A/H3N2); B/Ned/537/05 or B/HK/5/72 (data marked with #).

cCytotoxicity expressed as the minimum cytotoxic concentration (MCC; compound concentration producing minimal changes in cell morphology, as estimated by microscopy) or the 50% cytotoxic concentration (CC50; estimated by the MTS cell viability assay).

Data represent the means of two to five independent tests.