Table 1.

Estimated Ki values, inhibitory activity on NS5B, anti-HCV activity and cytotoxicity of the studied compounds

Cpds	R1	R2	R3	R4	R7	AutoDock Estimated Ki	NS5B functional assay	Replicon assay on Huh5-2
						Ki (µM)a	IC50 (µM)b	EC50 (µM)c	EC90 (µM)d	CC50 (µM)e	SIf
3	F	CF3	CH3	H	Cl	0.340	1.41±0.2	1.5	NDg	10.5	6.8
4	F	CF3	H	CH3	Cl	0.255	0.154±0.015	72.3	>192.3	>192.3	>2.5
5	H	Cl	H	Cl	Cl	0.249	NDg	>200	>200	>200	NDg
6	H	Cl	H	Cl		0.096	0.067±0.02	1.7	NDg	3.7	2.3
7	H	Cl	H	Cl		0.070	0.040±0.004	2.7	NDg	2.8	1.2
8	H	Cl	H	Cl		0.043	0.069±0.002	2.2	13.5	>244	>54
9	H	Cl	H	Cl		0.093	0.138 ± 0.023	8.6	NDg	>149	>17
10	H	Cl	H	Cl		0.178	6.132 ± 1.6	23.8	94.6	>147	>6
27						2.49	3.06± 0.6	31.3	NDg	>193	3.06
28						NCh	23.7 ± 6	7.3	NDg	>204	>28
2						0.652	0.211± 0.01 (0.008)i	2.02	4.7	42.3	21

^aAutoDock-predicted inhibition constant (Ki) for each selected IFD complex

^bIC₅₀ = concentration of compound that inhibits 50% enzyme activity in vitro. The IC₅₀ values of the compounds were determined from dose-response curves employing 8–12 concentrations of the indicated compounds in duplicate in two independent experiments ± SD.

^cEC₅₀ = the effective concentration required to inhibit virus replication by 50%. The reported values represent the means of data derived at least from three independent experiments.

^dEC₉₀ = the effective concentration required to inhibit virus replication by 90%. The reported value represents the means of data derived at least from three independent experiments.

^eCC₅₀ = is the concentration of compound exhibiting 50% antimetabolic effect as evaluated by the MTS assay. The reported value represents the means of data derived at least from three independent experiments.

^fSI = selectivity index (ratio of CC₅₀ to EC₅₀).

^gND = not determined.

^hNC= not calculated: the IFD top pose of this 6-aminoquinolone derivative showed that the compound was unable to properly occupy TSI.

ⁱIC₅₀ value reported by Kumar et al.¹⁷