Table 1.
Evaluation of anziaic acid and analogues against topoisomerases and whole cell bacteriaa
| |||||||
|---|---|---|---|---|---|---|---|
| Compound | MW (g/mol) | cLogPb |
E. coli Topo I inhibition IC50 (μM) |
Human Topo IIα inhibition IC50 (μM) |
E. coli DNA gyrase IC50 (μM) |
B. subtilis MIC (μM) |
E. coli MIC (μM) |
| 4 | 224.25 | 3.34 | 1000 | >1000 | >1000 | >200 | >200 |
| 6 | 700.86 | - | >1000 | >1000 | >1000 | >200 | >200 |
| Anziaic acid (isolated natural product)27 | 430.49 | 7.77 | 19 | 35 | 19 | 14 | 28 |
| Anziaic acid (synthetic sample) | 430.49 | 7.77 | 17.7 | 35 | 23.6 | 12.5 | 100 |
| 10c | 560.59 | 9.25 | >1000 | >1000 | >1000 | >200 | >200 |
| 11a | 360.36 | 5.15 | 500 | 250 | 250 | 50 | 200 |
| 11b | 360.36 | 6.05 | 250 | 125 | 250 | 50 | >200 |
| 11c | 290.23 | 3.44 | >1000 | >1000 | >1000 | >200 | >200 |
| 11d | 386.48 | 7.92 | 500 | 250 | 250 | 3.12 | 25 |
| 14 | 470.55 | 9.42 | >1000 | 500 | >1000 | 50 | >200 |
| 15 | 351.44 | 6.34 | >250 | n.d. | n.d. | 50–100 | 200 |
| 16 | 351.44 | 6.38 | >250 | n.d. | n.d. | 100 | 400 |
| 17 | 321.67 | 2.75 | >250 | n.d. | n.d. | >800 | >800 |
| 18 | 212.25 | 2.35 | 125–250 | n.d. | n.d. | 400 | 200–400 |
| 19 | 287.23 | 4.27 | 62.5–125 | n.d. | n.d. | 200 | 200 |
| 20 | 473.40 | 8.04 | >250 | n.d. | n.d. | >800 | >800 |
| 21 | 310.43 | 7.30 | >250 | n.d. | n.d. | >800 | >800 |
| 22 | 236.35 | 6.83 | >250 | n.d. | n.d. | >800 | >800 |
| 23 | 280.28 | 3.12 | >250 | n.d. | n.d. | >800 | >800 |
| 24 | 228.24 | 3.79 | >250 | n.d. | n.d. | >400 | >400 |
| 25 | 182.17 | 2.76 | >250 | n.d. | n.d. | >400 | >400 |
| 26 | 328.15 | 4.02 | >250 | n.d. | n.d. | 200 | 200 |
a
n.d.-not determined.
b
The n-octanol/water partition coefficient (LogP) of compounds was calculated using ChemBioOffice® Ultra version 12.0 from CambridgeSoft Corporation.