TABLE 1.
IC50s of the SP compounds on the polymerase and RNase H activities of HIV-1 RT and on the 3′ processing and transfer activities of HIV-1 IN
| Inhibitor | IC50 (μM [95% confidence interval])a
|
|||
|---|---|---|---|---|
| RT
|
IN
|
|||
| Polymerase | RNase H | 3′ Processing | Transfer | |
| Parent compound | ||||
| SP15 | 3.2 (2.6-3.9) | 20 (5.2-76) | 40 (11-140) | 11 (6.9-17) |
| Monosubstituted | ||||
| SP2 | 0.66 (0.34-1.3) | 14 (3.5-59) | 13 (9.6-18) | 2.6 (0.62-11) |
| SP47 | 2.3 (0.89-6.2) | 1.3 (0.6-3.1) | 0.71 (0.37-1.3) | 0.78 (0.30-2.0) |
| 0.36 (0.29-0.46)* | ||||
| SP4 | 2.7 (0.76-9.6) | 58 (38-90) | 13 (7.1-24) | 120 (7.1-210) |
| SP5 | 1.1 (0.47-2.8) | 18 (7.1-46) | 11 (7.6-16) | 5.3 (0.91-31) |
| SP46 | 0.57 (0.36-0.92) | 12 (5.6-28) | 0.57 (0.39-0.84) | 1.2 (0.44-3.5) |
| 0.25 (0.21-0.28)* | ||||
| SP1 | 20 (7.4-56) | 330 (91-1,200) | 200 (98-410) | 17 (6.4-46) |
| SP3 | 1.6 (0.39-6.9) | 59 (18-190) | 29 (4.1-210) | 7.1 (1.0-49) |
| SP6 | 25 (4.7-130) | 32 (25-43) | 54 (40-72) | 18 (6.2-50) |
| Disubstituted | ||||
| SP48 | 3.2 (0.53-18.7) | 46 (25-83) | 2.3 (1.7-3.2) | 3.1 (1.1-8.6) |
| SP7 | 51 (5.6-470) | 15 (6.2-35) | 3.2 (1.8-5.5) | 3.7 (0.74-18) |
| 1.2 (0.56-2.5)* | ||||
| SP8 | 170 (43-640) | 550 (58-5,200) | 8.8 (5.0-15) | 3.8 (1.2-12) |
| SP45 | 52 (27-99) | 900 (470-1,700) | 0.15 (0.075-0.28) | 1.7 (0.60-4.7) |
| SP9 | 1.2 (0.42-3.6) | 4.7 (1.2-18) | 3.1 (2.2-4.5) | 1.1 (0.23-5.4) |
| 1.4 (0.90-2.0)* | ||||
| C-7 modified | ||||
| SP10 | >1,000 | >1,000 | >1,000 | >1,000 |
| SP11 | >1,000 | >1,000 | >1,000 | >1,000 |
| Acetylated | ||||
| SP12 | 7.6 (6.9-8.3) | 65 (45-93) | 90 (24-340) | 62 (15-270) |
| SP20 | 30 (8.0-110) | 1,000 (980-1,100) | >1,000 | NDb |
| O-methylated | ||||
| SP13 | 190 (52-710) | 730 (200-2,600) | >1,000 | >1,000 |
| SP14 | 360 (220-590) | >1,000 | 700 (110-4,400) | >1,000 |
a
IC50s and 95% confidence intervals were determined from a single fit when the IC50 was >10 μM or from at least three measurements when the IC50 was <10 μM. All data were obtained with MgCl2, except those indicated by an asterisk, which were obtained with 10 mM MnCl2.
b
ND, not determined.