Table 1.
| Compound # |
Formal Name |
Compound Structure | Derivative series (a) |
Inhibition of HBV RNaseH |
HBV replication inhibition (EC50,μ3M) (e) |
HSV-1 suppression (log10 at 5 μM) (f) |
Inhibition of huRNaseH1 (b) |
Toxicity in HepDES19 (g) | TI | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Oligo- nucleotide directed cleavage assay (b, c) |
Molecular Beacon cleavage assay (d) |
MTS | NR | LDH | ||||||||
| 208 | Sun B8155 |
|
HPD | + | + | 0.69 ± 0.2 | − | − | 15 ± 7 | 13 ± 1 | 12 ± 0.1 | 22 |
| 211 | Rilopirox |
|
HPD | − | − | − | − | − | ||||
| 86 | VS42 |
|
HID | − | − | 1.4 ± 0.3 | − | + | 99 ± 2 | 52 ± 11 | >100 | 71 |
| 83 | MB88 |
|
HID | − | + | 2.3 ± 1.6 | − | + | 100± 35 | >100 | >100 | 43 |
| 88 | VS45 |
|
HID | − | − | 2.5 ± 0.5 | − | + | 40 ± 6 | 26 ± 2 | 57 ± 6 | 16 |
| 89 | VS51 |
|
HID | − | − | 2.6 ± 0.8 | − | + | 28 ± 8 | 19 ± 3 | 25 ± 4 | 11 |
| 1 | TRC 939800 |
|
HID | + | + | 4.2 ± 1.4 (b) | − | + | 75 ± 24 | 81 ± 4 | 79 ± 12 | 18 |
| 81 | MB4 |
|
HID | − | + | 4.4 ± 3.0 | − | + | 57 ± 16 | 31 ± 7 | 24 ± 5 | 13 |
| 91 | MB106 |
|
HID | − | − | 4.6 ± 1.0 | − | + | 11 ± 4 | 33 ± 3 | 58 ± 22 | 2.4 |
| 87 | VS55 |
|
HID | − | − | 4.5 ± 3.7 | − | + | 37 ± 17 | 24 ± 1 | 52 ± 15 | 8.2 |
| 85 | MB103 |
|
HID | − | − | 6.5 ± 1.5 | − | + | 29 ± 12 | 67 ± 13 | >100 | 4.5 |
| 84 | MB105 |
|
HID | − | − | 6.5 ± 4.5 | − | + | 23 ± 9 | 32 ± 8 | 37 ± 15 | 3.5 |
| 90 | MB104 |
|
HID | − | − | 19 ± 0.9 | − | + | 88 ± 17 | >100 | >100 | 4.6 |
| 82 | MB71 |
|
HID | − | − | − | + | |||||
| 78 | MB1 |
|
HID | − | − | − | + | |||||
| 79 | MB2 |
|
HID | − | − | − | − | |||||
| 80 | MB3 |
|
HID | − | − | − | − | |||||
| 41 | TRC C432800 (Ciclopirox) |
|
POH | − | − | 5.0 | + | |||||
| 42 | Labotest 72543251 |
|
POH | − | − | − | + | |||||
| 43 | Sigma PH008969 |
|
POH | − | − | − | − | |||||
| 44 | Labotest 12243782 |
|
POH | − | − | − | − | |||||
| 45 | TCI America H1040 |
|
HID | − | − | − | − | |||||
| 128 | Aldrichselect CNC_ID100615760 |
|
POH | − | − | − | − | |||||
| 132 | Aldrichselect CNC_ID 389306767 |
|
POH | − | − | |||||||
| 138 | Sigma H53704 |
|
POH | − | − | − | − | − | ||||
| 139 | Sigma 130672 |
|
POH | − | − | − | ||||||
| 140 | Chembridge 6325462 |
|
POH | − | − | − | + | |||||
| 191 | Piroctone olamine |
|
POH | − | − | 4.6 | − | |||||
| 197 | Benzoylene urea |
|
POH | − | − | − | − | |||||
| 198 | 2,3-dihydroxy-quinoxaline |
|
POH | − | − | − | − | |||||
| 204 | AK-830/13217043 |
|
POH | − | − | − | + | |||||
| 206 | AJ-333/25006202 |
|
POH | − | − | − | + | |||||
| 217 | Visas M Lab 444035142 |
|
POH | − | − | − | + | |||||
| 236 | ZF4 |
|
FLT | − | − | − | − | |||||
| 237 | ZF13 |
|
FLT | − | − | − | ||||||
| 238 | ZF18 |
|
FLT | − | − | − | ||||||
| 239 | ZF19 |
|
FLT | − | − | − | ||||||
| 240 | ZF24 |
|
FLT | − | − | − | + | |||||
| 241 | ZF29 |
|
FLT | − | − | − | ||||||
(a)
N-hydroxyisoquinolinedione (HID), polyoxygenated heterocycles (POH), N-hydroxypyridinediones (HPD), and flutimides (FLT)
(b)
Compounds 1–91, and 138–140 previously reported in (Cai et al., 2014)
(c)
(+), Dose-dependent inhibition at ≤100 μM; (−), No inhibition detected at 100 μM
(d)
(+), Dose-dependent inhibition at ≤500 μM; (−), No inhibition detected at 500 μM
(e)
(−), No inhibition detected at 20 μM
(f)
(−), ≤1 log10 suppression of plaque forming units at 5 μM
(g)
CellTiter 96 Aqueous Non-Radioactive Cell Proliferation Assay (MTS), neutral red retention assay (NR), lactate dehydrogenase release (LDH)