Arsinothricin and methods of treating infections using arsinothricin
View Patent ↗Certain embodiments of the invention pertain to a method of treating an infection in a subject caused by an infectious agent other than Escherichia coli , the method comprising administering to the subject arsinothricin or a salt thereof. The infectious agent other than E. coli can be a bacterium, protozoan, helminth, archaebacterium, or a fungus. In preferred embodiments, the infectious agent is Mycobacterium tuberculosis, Mycobacterium bovis , or Enterobacter cloacae . The invention also pertains to a method of treating an infection in a subject caused by an infectious agent, comprising administering to the subject arsinothricin or a salt thereof in combination with an inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase. In certain such embodiments, the infectious agent expresses phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase. Further embodiments provide compositions comprising arsinothricin or a salt thereof and an inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase.
1. A method of treating an infection in a subject caused by Mycobacterium tuberculosis that expresses arsinothricin N-acetyltransferase or Mycobacterium bovis that expresses arsinothricin N-acetyltransferase, comprising administering to the subject arsinothricin or a salt thereof and an inhibitor of arsinothricin N-acetyltransferase.
2. The method of claim 1 , wherein the infection is caused by Mycobacterium tuberculosis.
3. A method of treating a bacterial infection in a subject caused by an infectious bacterial agent, comprising administering to the subject a composition comprising arsinothricin or a salt thereof and an inhibitor of arsinothricin N-acetyltransferase.
4. The method of claim 3 , wherein the infectious agent is Escherichia coli, Burkolderia gladioli, Sinorhizobium meliloti, Schewanella putrefaciens, Bacillus cereus, Bacillus megaterium, Corynebacterium glutamicum, Mycobacterium bovis, Mycobacterium tuberculosis , carbapenem-resistant Acinetobacter baumannii , carbapenem-resistant Pseudomonas aeruginosa , carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus faecium , methicillin and/or vancomycin-resistant Staphylococcus aureus , clarithromycin-resistant Helicobacter pylori , fluoroquinolone-resistant Campylobacter spp., fluoroquinolone-resistant Salmonellae, cephalosporin and/or fluoroquinolone-resistant Neisseria gonorrhoeae , penicillin-non-susceptible Streptococcus pneumoniae , ampicillin-resistant Haemophilus influenzae , fluoroquinolone-resistant Shigella spp. or carbapenem-resistant Enterobacter cloacae.
5. A method of treating a bacterial infection in a subject caused by an infectious bacterial agent that expresses arsinothricin N-acetyltransferase other than Escherichia coli , the method comprising administering to the subject arsinothricin or a salt thereof.
6. The method of claim 5 , comprising administering arsinothricin or salt thereof via oral, pulmonary, buccal, suppository, intravenous, intraperitoneal, intranasal, intramuscular, or subcutaneous route.
7. The method of claim 5 , wherein the infectious agent other than Escherichia coli is Burkolderia spp., Sinorhizobium spp., Schewanella spp., Bacillus spp., Corynebacterium spp., Mycobacterium spp., or Enterobacter spp.
8. The method of claim 5 , wherein the infectious agent other than Escherichia coli is Burkolderia gladioli, Sinorhizobium meliloti, Schewanella putrefaciens, Bacillus cereus, Bacillus megaterium, Corynebacterium glutamicum, Mycobacterium bovis, Mycobacterium tuberculosis , carbapenem-resistant Acinetobacter baumannii , carbapenem-resistant Pseudomonas aeruginosa , carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus faecium , methicillin and/or vancomycin-resistant Staphylococcus aureus , clarithromycin-resistant Helicobacter pylori , fluoroquinolone-resistant Campylobacter spp., fluoroquinolone-resistant Salmonellae, cephalosporin and/or fluoroquinolone-resistant Neisseria gonorrhoeae , penicillin-non-susceptible Streptococcus pneumoniae , ampicillin-resistant Haemophilus influenzae , or fluoroquinolone-resistant Shigella spp., or carbapenem-resistant Enterobacter cloacae.
9. The method of claim 5 , wherein the method further comprises administering to the subject an inhibitor of arsinothricin N-acetyltransferase.
10. The method of claim 9 , wherein the inhibitor of arsinothricin N-acetyltransferase is:
2-({8-fluoro-5H-pyridazino[4,5-b]indol-4-yl}sulfanyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl) acetamide; 3-oxo-N-({1-phenyl-1H,4H,5H,6H-cyclopenta[c]pyrazol-3-yl}methyl)-3,4-dihydro-2H-1,4-benzothiazine-6-carboxamide; 1-(4-fluorobenzoyl)-N-(3-phenyl-1H-pyrazol-4-yl) piperidine-3-carboxamide; N-[3-({[(6-fluoro-3,4-dihydro-2H-1-benzopyran-4-yl) carbamoyl]amino}methyl) phenyl]cyclobutanecarboxamide; or 1-[1-(2-fluorobenzoyl) piperidin-4-yl]-3-[2-(3-fluorophenyl) cyclopropyl]urea.
11. The method of claim 5 , further comprising isolating the infectious agent, testing the infectious agent for the expression of arsinothricin N-acetyltransferase, and administering to the subject an inhibitor of arsinothricin N-acetyltransferase.
12. The method of claim 11 , wherein the inhibitor of arsinothricin N-acetyltransferase is:
2-({8-fluoro-5H-pyridazino[4,5-b]indol-4-yl}sulfanyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl) acetamide; 3-oxo-N-({1-phenyl-1H,4H,5H,6H-cyclopenta[c]pyrazol-3-yl}methyl)-3,4-dihydro-2H-1,4-benzothiazine-6-carboxamide; 1-(4-fluorobenzoyl)-N-(3-phenyl-1H-pyrazol-4-yl) piperidine-3-carboxamide; N-[3-({[(6-fluoro-3,4-dihydro-2H-1-benzopyran-4-yl) carbamoyl]amino}methyl) phenyl]cyclobutanecarboxamide; or 1-[1-(2-fluorobenzoyl) piperidin-4-yl]-3-[2-(3-fluorophenyl) cyclopropyl]urea.
13. The method of claim 5 , wherein the infectious agent is Mycobacterium tuberculosis, Mycobacterium bovis , or carbapenem-resistant Enterobacter cloacae.