Table 1.
Anti-HIV and anti-EV71 activity of the synthesized compounds.
| Compound | HIV-1 EC50a,c (μM) | HIV-2 EC50a,c (μM) | CC50b,c (μM) | EV71 EC50a,d (μM) | EV71 EC90e,d (μM) | CC50b,d (μM) |
|---|---|---|---|---|---|---|
| Ia | 1.9 ± 0.2 | 6.8 ± 5.8 | >100 | 27.1 | ND | >60 |
| Ib | 10 ± 6 | >100 | >100 | >82.2 | ND | >82 |
| Ic | 5.2 ± 2 | >100 | >100 | >85.1 | ND | >85 |
| Id | 3.6 ± 0.0 | >100 | >100 | 20.5 | ND | >57 |
| IIa | 0.2 ± 0.01 | 3.2 ± 0.10 | >100 | 0.20 ± 0.02 | 0.57 ± 0.03 | >19 |
| IIb | 1.1 ± 0.10 | 3.9 ± 0.30 | >100 | 1.44 ± 0.14 | 2.67 ± 0.05 | >26 |
| IIc | 1.0 ± 0.02 | 1.4 ± 0.02 | >100 | 1.51 ± 0.14 | 2.60 ± 0.19 | >27 |
| IId | 1.1 ± 0.30 | 1.3 ± 0.02 | >100 | 0.52 ± 0.03 | 0.95 ± 0.04 | >27 |
| 1 | 2.3 ± 0.30 | 6.6 ± 7.7 | >100 | 0.3 ± 0.10 | 0.5 ± 0.10 | >25 |
| DS-5000 | 0.07 ± 0.02 | 0.03 ± 0.01 | >20 | ND | ND | ND |
| PRM-A | 3.3 ± 1.2 | 5.9 ± 3.7 | >100 | ND | ND | ND |
| Pirodavir | ND | ND | ND | 0.3 ± 0.10 | 0.6 ± 0.2 | >100 |
Cell-based activity and toxicity assays were performed to determine EC50 and CC50 of selected compounds in the context of HIV and EV71 infection (see supplementary information for detailed protocols). Briefly, for EV71 RD cells were seeded in 96-well plate and infected at an MOI of 0.1. Decreasing concentration of compound were applied concomitantly with virus (1:3 dilution, concentration range 100 μM–0.1 μM). Cells were harvested at 3 days post infection and the virus-induced CPE inhibition was measured by MTS assay.
Data are the mean ± S.D. of 3 independient experiments in the two different susceptible cell types MT-4 and RD cells.
ND: Not Determined.
EC50: 50% Effective concentration, or the concentration required to inhibit virus-induced cytopathicity by 50%.
CC50: 50% Cytostatic concentration, or the concentration required to inhibit host cell viability by 50%.
In MT-4 cultures.
In RD cultures.
EC90: concentration of compound at which the EV71-induced cytopathic effect is reduced by 90%.