Table 1. Anti-HCV activity, selectivity, and anti-histamine properties of CCZ analogs.

Compounds were tested in the HCV-Luc infection assay in parallel with the ATPlite assay. HCV-Luc was used to infect Huh7.5.1 cells in the presence of compound titration. Viral infection and replication were measured by luciferase signal 48 hours after treatment, and cytotoxicity was evaluated by the adenosine 5′-triphosphate (ATP)-based cell viability assay. The concentration values that led to 50% and 90% viral inhibition (EC50 and EC90, respectively) and 50% cytotoxicity (CC50) were calculated with GraphPad Prism using a nonlinear regression equation. Cyclosporin A was a control. Data are means ± SEM from n ≥ 3 independent experiments. Antihistamine activity was obtained with the β-arrestin H1-histamine receptor assay. N.D., not determined.

CompoundHCV-Luc EC50 (μM)HCV-Luc EC90 (μM)ATPlite CC50 (μM)SIAntihistamine activity at 10 nM (%)
Racemic CCZ0.044 ± 0.0111.40 ± 0.4549.8 ± 17.299472.60
(R)-CCZ0.020 ± 0.0051.09 ± 0.3737.5 ± 4.15187588.00
(S)-CCZ0.024 ± 0.0091.44 ± 0.4333.4 ± 2.44139241.70
(S)-Nor-CCZ0.034 ± 0.0120.578 ± 0.0999.31 ± 0.042742.24
Cyclosporin A0.213 ± 0.0440.92 ± 0.20N.D.N.D.N.D.