N-alkylthio beta-lactams, alkyl-coenzyme A asymmetric disulfides, and aryl-alkyl disulfides as anti-bacterial agents
The present invention provides N-alkylthio β-lactams and disulfide compounds (e.g., alkyl-coenzyme A asymmetric disulfides or aryl-alkyl disulfides), compositions containing such compounds, and methods of their use as anti-bacterial agents.
1. A method for inhibiting the growth of a bacterium, comprising contacting the bacterium with an effective amount of an N-alkylthio beta-lactam, or applying the N-alkylthio beta-lactam to a surface that may come in contact with the bacterium, wherein the N-alkylthio beta-lactam has the chemical structure of compound 8,
or a pharmaceutically acceptable salt or hydrate thereof, wherein R is C 2 -C 15 alkyl, wherein R′ is —CH 3 , and wherein R″ is
or wherein the N-alkylthio beta-lactam is compound 2g,
or a pharmaceutically acceptable salt or hydrate thereof.
2. The method of claim 1 , wherein the bacterium is a Bacillus spp., a Staphylococcus spp., aMicrococcus spp., a Streptococcus spp., a Neisseria spp., or a Streptomyces spp.
3. The method of claim 1 , wherein the bacterium is Bacillus anthracis, Staphylococcus aureus, Mycobacterium tuberculosis , or Escherichia coli.
4. The method of claim 1 , wherein the bacterium is methicillin-resistant Staphylococcus aureus (MRSA).
5. The method of claim 1 , wherein the bacterium is contacted in vitro or in vivo with the N-alkylthio beta-lactam.
6. The method of claim 1 , wherein the surface is a work surface, a table, a surgical instrument, or an implant or device to be placed in or on the body of a subject, or an eating or cooking utensil.
7. The method of claim 6 , wherein the implant or device is a stent, catheter, access port, intravenous delivery tube, heart valve, dental implant, electro-mechanical device, prosthetic device, glucose sensor, or stabilizing device.
8. The method according to claim 1 , wherein the N-alkylthio beta-lactam has the chemical structure of compound 8
or a pharmaceutically acceptable salt or hydrate thereof, wherein R is C 2 -C 15 alkyl, wherein R′ is —CH 3 , and wherein R″ is
9. The method according to claim 1 , wherein the N-alkylthio beta-lactam is compound 2g
or a pharmaceutically acceptable salt or hydrate thereof.
10. A method for treating an infection by a bacterium, comprising administering to a subject in need thereof an effective amount of an N-alkylthio beta-lactam, wherein the N-alkylthio beta-lactam has the chemical structure of compound 8
or a pharmaceutically acceptable salt or hydrate thereof, wherein R is C 2 -C 15 alkyl, wherein R′ is —CH 3 , and wherein R″ is
or wherein the N-alkylthio beta-lactam is compound 2g
or a pharmaceutically acceptable salt or hydrate thereof.
11. The method of claim 10 , wherein the bacterium is a Bacillus spp., a Staphylococcus spp., a Micrococcus spp., a Streptococcus spp., a Neisseria spp., or a Streptomyces spp.
12. The method of claim 10 , wherein the bacterium is Bacillus anthracis, Staphylococcus aureus, Mycobacterium tuberculosis , or Escherichia coli.
13. The method of claim 1 , wherein the bacterium is methicillin-resistant Staphylococcus aureus (MRSA).
14. The method of claim 10 , wherein the subject is a human.
15. The method of claim 10 , wherein the N-alkylthio beta-lactam is administered to the subject orally or parenterally, or intravenously, intraperitoneally, intramuscularly, topically, or subcutaneously.
16. The method according to claim 10 , wherein the N-alkylthio beta-lactam has the chemical structure of compound 8
or a pharmaceutically acceptable salt or hydrate thereof, wherein R is C 2 -C 15 alkyl, wherein R′ is —CH 3 , and wherein R″ is
17. The method according to claim 10 , wherein the N-alkylthio beta-lactam is compound 2g
or a pharmaceutically acceptable salt or hydrate thereof.