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Compound R1 R3 R4 R6 R7 HIV-1 infectivity (%) Cell survival rate (%) 1 -CH2CH2N pyrrolidine OMe OMe OMe OMe 3.62±0.27 88.07±1.88 2 -CH2CH2N piperidine OMe OMe OMe OMe 16.61±7.37 107.46±9.21 3 -CH2CH2N-(CH2CH3)2 OMe OMe OMe OMe 47.78±4.35 86.89±1.97 4 -CH2CH2N-(CH2CH3)2 OMe OMe H H 42.71±3.95 103.37±5.57 5 -CH2CH2N piperidine OMe OMe OMe H 0.98±0.27 106.63±11.69 6 -CH2CH2N piperidine OMe OMe H H 8.32±0.51 95.84±2.26 7 -CH2CH2N piperidine NH2 H H H 18.69±0.00 74.18±1.17 8 -CH2CH2N piperidine OMe OMe H F 0.48±024 85.50±7.76 9 -CH2CH2N piperidine OMe OMe H Cl 1.65±0.25 93.67±2.12 Seliciclib 45.01±1.99 103.57±4.30 ID 262860 29.35±1.33 46.34±0.93 The inhibitory effects on HIV-1 infection and cell viability were determined in TZM-bl cells infected with HIV-1NL4-3 at an MOI of 1. Table 1. Structure and inhibitory effect of aristolactam derivatives 1–9 on HIV-1 infection.
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Compound IC50 (μmol/L)a CC50 (μmol/L)b SIc 1 0.69 ± 0.09 6.88 ± 0.31 9.94 2 1.03 ± 0.38 16.91 ± 3.22 16.45 3 3.73 ± 1.00 17.15 ± 0.34 4.59 4 3.07 ± 0.22 6.98 ± 0.09 2.27 5 1.07 ± 0.06 4.51 ± 0.96 4.23 6 1.06 ± 0.03 4.97 ± 0.62 4.70 7 2.00 ± 0.61 3.62 ± 0.15 1.80 8 0.55 ± 0.01 3.72 ± 0.01 6.74 9 0.44 ± 0.01 3.64 ± 0.08 8.31 Seliciclib 2.29 ± 0.40 25.49 ± 0.17 11.11 The inhibitory effects on HIV-1 infection and cell viability were determined in TZM-bl cells infected with HIV-1NL4-3 at an MOI of 1.
aIC50: half-maximal inhibitory concentration.
b CC50: concentration that reduces cell viability by 50%.
cSI: selectivity index, i.e. the ratio of IC50 to CC50.Table 2. Concentration–responses of aristolactam derivatives on cytotoxicity and anti-HIV activity.
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Compound IC50 (μmol/L)a 1 1.11 ± 0.02 2 2.85 ± 0.17 3 2.58 ± 0.05 4 3.40 ± 0.02 5 1.36 ± 0.01 6 2.47 ± 0.26 7 1.78 ± 0.15 8 2.25 ± 0.24 9 3.38 ± 0.05 Seliciclib 2.25 ± 0.14 aThe compounds were assessed in bl-DTR cells using a concentration–response test. Table 3. Concentration–responses of aristolactam derivatives on the inhibition of Tat-induced HIV-1 transcription.
Figure 5 个
Table 3 个