Table 3.
In vitro activity of riminophenazine analogs against drug-resistant clinical isolates of M. tuberculosis
| Compound | MIC (μg/ml)a |
||
|---|---|---|---|
| Range | MIC50 | MIC90 | |
| TBI-161 | 0.029–0.081 | 0.052 | 0.054 |
| TBI-166 | 0.027–0.095 | 0.058 | 0.080 |
| TBI-416 | 0.025–0.076 | 0.037 | 0.060 |
| TBI-443 | 0.030–0.061 | 0.059 | 0.060 |
| TBI-444 | 0.031–0.060 | 0.056 | 0.060 |
| TBI-449 | 0.050–0.114 | 0.082 | 0.104 |
| TBI-450 | 0.031–0.062 | 0.051 | 0.062 |
| TBI-678 | 0.050–0.092 | 0.061 | 0.081 |
| TBI-688 | 0.030–0.089 | 0.051 | 0.063 |
| TBI-1002 | 0.051–0.110 | 0.062 | 0.102 |
| TBI-1004 | 0.058–0.121 | 0.094 | 0.112 |
| TBI-1010 | 0.015–0.054 | 0.015 | 0.027 |
| CFM | 0.108–0.240 | 0.219 | 0.221 |
| INH | 1.0–40 | 20 | 40 |
| RIF | 1.0–40 | 20 | 40 |
| LVFX | 0.05–10 | 1 | 10 |
MIC50 and MIC90 refer to the MICs at which 50 and 90% of the isolates, respectively, are inhibited. The MIC of each compound was evaluated for the following 10 clinical isolates with varying drug resistance profiles, including both MDR and XDR strains: isolate 118, resistant to INH, SM, RIF, RPT, PTO, OFX, and LVFX; isolate 040, resistant to INH, RIF, PTO, RPT, OFX, and LVFX; isolate 002, resistant to INH, RIF, and SM; isolate 004, resistant to SM, RIF, RPT, KM, and OFX; isolate 057, resistant to RIF, RPT, OFX, and LVFX; isolate 054, resistant to INH, RIF, and RPT; isolate 109, resistant to INH, EMB, RIF, KM, CAP, PTO, OFX, LVFX, and RPT; isolate 062, resistant to INH, RIF, RPT, KM, PTO, and OFX; isolate 1104, resistant to INH, RIF, and OFX; and isolate 1109, resistant to INH, RIF, and OFX. Abbreviations: INH, isoniazid; RIF, rifampin; EMB, ethambutol; SM, streptomycin; RPT, rifapentine; OFX, ofloxacin; PAS, p-aminosalicylic acid; CAP, capreomycin; KM, kanamycin sulfate; PTO, protionamid; LVFX, levofloxacin.