Rifalazil (ABI-1648; KRM-1648) 是利福霉素衍生物，可抑制细菌依赖 DNA 的 RNA 聚合酶 (RNA polymerase) 并阻断 RNA 聚合酶中的 β 亚基从而杀死细菌感染的细胞。Rifalazil (ABI-1648; KRM-1648) 是一种抗生素 (antibiotic)，对分枝杆菌，革兰氏阳性细菌，幽门螺杆菌，肺炎衣原体和沙眼衣原体有抑制作用，其 MIC 值在 0.00025 至 0.0025 μg/ml 之间。Rifalazil (ABI-1648; KRM-1648) 有潜力用于衣原体感染，梭菌相关性腹泻菌感染 (CDAD) 和结核病 (TB) 研究的相关研究。
Rifalazil exhibits antimicrobal activity against Gram-positive enteric bacteria, inhibits
Clostridium difficile
,
Clostridium perfringens
,
Bacteroides fragilis
with MIC
50
value of 0.0015, 0.0039, 0.0313 µg/ml, respectively.
Rifalazil exhibits antimicrobal activity against Gram-negative enteric bacteria, inhibits
Escherichia coli
and
Klebsiella pneumoniae
with MIC
50
value of 16 and 16 µg/ml, respectively.
Rifalazil exhibits antimicrobal activity against non-enteric Gram-positive bacteria, inhibits Methicillin-susceptible
Staphylococcus aureus
, Methicillin-resistant
S. aureus
, Methicillin- and quinolone-resistant
S. aureus
,
Staphylococcus epidermidis
,
Streptococcus pyogenes
, Streptococcus pneumoniae with MIC
50
value of 0.0078, 0.0078, 0.0078, 0.0078, 0.0002, 0.0001 µg/ml, respectively.
Rifalazil exhibits antimicrobal activity against
Helicobacter pylori
,
Chlamydia pneumoniae
and
Chlamydia trachomatis
with MIC
50
value of 0.004, 0.000125 and 0.00025 µg/ml, respectively.
Rifalazil (oral gavage; 20, 25, and 150 mg/kg; 6-8 weeks) combines with isoniazid (INH) for 6 weeks or greater significantly reduced the number of mice per group in which
M. tuberculosis
is detected in both spleens and lungs compared to the reductions for the early and late controls. And the addition of Pyrazinamide (PZA) does not significantly improve RLZ-INH therapy at any time point.
|
Animal Model:
|
Female CD-1 mice infected with 5.2 × 10
7
viable mycobacteria
|
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Dosage:
|
20, 25, and 150 mg/kg; 6-8 weeks
|
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Administration:
|
Oral gavage
|
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Result:
|
Combined with isoniazid (INH) showed its potential for short-course treatment of
Mycobacterium tuberculosis
infection.
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