. Author manuscript; available in PMC: 2016 Sep 10.

Published in final edited form as: J Med Chem. 2015 Aug 25;58(17):6994–7006. doi: 10.1021/acs.jmedchem.5b00900

Table 2.

Antiviral Activity of 25f, 25i and 25j against Multidrug Resistant HIV-1 Variants.

Virus	DRV	EC₅₀ ± SD, (μM) (fold change)^a,^b		Inhibitor 25j
Virus	DRV	Inhibitor 25f	Inhibitor 25i	Inhibitor 25j
HIV-1_NL4-3	0.0026 ±0.0006	0.029 ±0.003	0.015 ±0.003	0.001 ±0.0033
HIV-1_DRV R_P10	0.031 ±0.005 (12)	nd	0.039 ±0.009 (2.6)	0.021 ±0.004 (21)
HIV-1_DRVR_P20	0.097 ±0.051 (37.3)	0.032 ±0.003 (1.1)	nd	0.024 ±0.013 (23)
HIV-1_DRV R_p51	3.5 ±1.4 (1346)	nd	0.23 ±0.08 (15)	0.26 ±0.12 (260)

MT-4 cells (1 × 10⁴) were exposed to 50 TC1D₅₀^S of wild-type HIV-l_NL4-3, HIV-1_DRV^R_P10, HIV-l_DRV^R_P20, or HIV-l_DRV^R_P51 and cultured in the presence of various concentrations of each PI, and the IC₅₀ values were determined using the XTT assay. The amino acid substitutions identified in protease of HIV-l_DRV^R_P10, HIV-l_DRV^R_P20 and HIV-l_DRV^R_P51 compared to HIV-1_NL4-3 include L101/I15V/K20R/L241/V321/M361/M46L/L63P/V82A/L89M; L101/115V/K20R/L241/V321/M361/M46L/L63P/A71T/V82A/L89M and L101/115V/K20R/L241/V321/L33F/M36I/M46L/I54M/L63P/K70Q/V82I/I84V/L89M, respectively.

All assays were conducted in triplicate, and the data shown respresent mean values (±1 standard deviation) derived from the results of two independent experiments. nd, not determined.