Table 6.
RpMetAP Inhibitory Compounds Tested in EC Culture Infection Model
| Compound | MW a | Stock (mM) b | Test Range (µM) c | Growth Inhibition d |
|---|---|---|---|---|
| (10) | 222.63 | 100 | 300, 30, 3, 0.3 | No |
| (11) | 257.07 | 100 | 300, 30, 3, 0.3 | No |
| (12) | 206.27 | 100 | 300, 30, 3, 0.3 | Yes |
| (13) | 220.30 | 100 | 300, 30, 3, 0.3 | Yes |
| (14) | 224.26 | 100 | 300, 30, 3, 0.3 | Yes |
| (15) | 240.72 | 100 | 300, 30, 3, 0.3 | Yes |
| (16) | 240.72 | 100 | 300, 30, 3, 0.3 | Yes |
| (17) | 275.16 | 100 | 30, 3, 0.3, 0.03 | No |
| (18) | 248.35 | 100 | 30, 3, 0.3, 0.03 | No |
| (19) | 262.37 | 100 | 30, 3, 0.3, 0.03 | No |
| (20) | 195.65 | 100 | 3, 0.3, 0.03, 0.003 | No |
| (21) | 181.62 | 100 | 30, 3, 0.3, 0.03 | Yes |
| (22) | 245.06 | 100 | 30, 3, 0.3, 0.03 | Yes |
| (23) | 190.16 | 100 | 3, 0.3, 0.03, 0.003 | No |
| (24) | 315.20 | 40 | 20, 2, 0.2, 0.02 | No |
| (25) | 362.25 | 25 | 7.5, 0.75, 0.075, 0.0075 | No |
| (26) | 325.75 | 100 | 3, 0.3, 0.03, 0.003 | Yes |
a
Compound Molecular Weight in g/mol.
b
Stock inhibitor solutions were initially prepared in 100% DMSO to achieve a 100 mM concentration. Compounds that were insoluble at 100 mM were adjusted by addition of DMSO until solubility was achieved.
c
All compounds were initially tested for toxicity against uninfected ECs. Working concentration test ranges that produced no EC toxicity were selected for further testing against R. prowazekii-infected ECs.
d
Inhibition of rickettsial growth was determined using the in vitro host EC viability assay described in the Experimental Methods section.