TABLE 1.
Effects of naphthoquinone drugs on incorporation in vitro of radiolabeled p-hydroxybenzoate into P. carinii ubiquinonea
| Drug and concn (μM) | Radioactivity (dpm)b | Incorporation of PHBA into CoQ (pmol/mg of protein)c |
|---|---|---|
| Atovaquoned | ||
| 0 | 5,221–5,684 | 151.8 ± 2.4 |
| 0.01 | 2,037–2,516 | 59.3 ± 2.0 |
| 0.02 | 3,263–3,453 | 92.8 ± 1.0 |
| 0.1 | 5,815–6,668 | 170.5 ± 4.3 |
| 0.2 | 5,205–6,105 | 155.3 ± 5.4 |
| 1.0 | 2,458–2,905 | 74.3 ± 2.1 |
| Diospyrine | ||
| 0 | 525–1,037 | 66.0 ± 4.3 |
| 0.01 | 468–1,105 | 58.1 ± 6.5 |
| 0.05 | 495–832 | 56.2 ± 3.3 |
| 0.1 | 389–974 | 56.7 ± 5.1 |
| 0.5 | 411–1,042 | 56.5 ± 8.0 |
| 1 | 468–1,168 | 65.5 ± 6.3 |
| 5 | 474–1,200 | 63.2 ± 7.8 |
| 10 | 498–1,168 | 66.5 ± 6.2 |
| 25 | 403–1,037 | 59.9 ± 6.0 |
| 50 | 394–921 | 58.6 ± 4.6 |
| 100 | 442–1,105 | 60.6 ± 6.5 |
| Diospyrin dimethylethere | ||
| 0 | 252–397 | 48.2 ± 3.7 |
| 0.01 | 205–242 | 45.9 ± 1.9 |
| 0.05 | 237–435 | 53.9 ± 5.6 |
| 0.1 | 232–446 | 46.2 ± 2.5 |
| 0.5 | 137–382 | 46.7 ± 7.7 |
| 1 | 177–347 | 43.9 ± 5.2 |
| 5 | 226–279 | 51.5 ± 2.6 |
| 10 | 247–421 | 49.3 ± 4.8 |
| 25 | 253–381 | 46.6 ± 4.9 |
| 50 | 242–392 | 45.8 ± 3.4 |
| 100 | 221–432 | 46.4 ± 4.6 |
| Diospyrin dimethylether hydroquinonee | ||
| 0 | 274–689 | 58.2 ± 10.9 |
| 0.01 | 523–679 | 79.6 ± 5.0 |
| 0.05 | 295–453 | 63.9 ± 9.1 |
| 0.1 | 342–568 | 56.2 ± 6.3 |
| 0.5 | 418–621 | 63.0 ± 7.4 |
| 1 | 379–584 | 53.2 ± 6.4 |
| 5 | 442–668 | 77.2 ± 7.5 |
| 10 | 368–768 | 62.4 ± 10.6 |
| 25 | 354–820 | 61.1 ± 12.0 |
| 50 | 361–558 | 56.4 ± 7.2 |
| 100 | 279–515 | 48.5 ± 5.4 |
Purified organisms were incubated for 2 days in 10 ml of serum-free RPMI 1640 medium containing [U-14C]p-hydroxybenzoate and various concentrations of a drug. Values are means ± standard errors of the means.
Values are ranges of radioactivity in the ubiquinone band isolated by TLC.
Protein content of organisms prior to incubation.
Organisms were incubated with 10 μCi of the substrate (n = 4).
Organisms were incubated with 5 μCi of the substrate (n = 6 except in the assays with 0.01 and 5 μM, in which n = 3).