Ecteinamycin, compositions and uses thereof
An isolated or synthesized compound of Formula I and salts thereof are provided. A compound isolated from Actinomadura and having a chemical formula of C 38 H 60 O 12 is also provided. Compositions including the compounds and methods of using the compounds to treat bacterial infections including gram positive infections such as C. difficile are also disclosed.
1. A method of treating a bacterial infection comprising administering to a mammal in need thereof an effective amount of a compound of Formula I:
a salt thereof, or a pharmaceutical composition comprising the effective amount of the compound of Formula I or salt thereof and a pharmaceutically acceptable carrier, wherein the effective amount is effective for treating the bacterial infection in the mammal.
2. The method of claim 1 , wherein the mammal is human.
3. The method of claim 1 , wherein the bacterial infection is caused by one or more of Clostridium, Staphylococcus , and Enterococcus.
4. The method of claim 1 , wherein the bacterial infection is caused by one or more of C. difficile, S. aureus , methicillin-resistant S. aureus , vancomycin-resistant Enterococcus, P. aeruginosa , and Kelbsiella pneumonia.
5. The method of claim 1 , wherein a second antibiotic other than the compound of Formula I is administered to the mammal in need thereof simultaneously, sequentially or separately with the compound of Formula I, the salt thereof or the pharmaceutical composition.
6. The method of claim 5 , wherein the second antibiotic is a beta-lactam or protein synthesis inhibitor.
7. A method of disrupting ion transport in bacteria, comprising contacting bacteria with an effective amount of a compound of Formula I:
a salt thereof, or with a pharmaceutical composition comprising the effective amount of the compound of Formula I or salt thereof and a pharmaceutically acceptable carrier, wherein the effective amount of the compound disrupts ion transport in the bacteria.
8. The method of claim 7 , wherein the bacteria comprises one or more of Clostridium, Staphylococcus, and Enterococcus.
9. The method of claim 7 , wherein the bacteria comprises one or more of C. difficile, S. aureus , methicillin-resistant S. aureus , vancomycin-resistant Enterococcus, P. aeruginosa , and Kelbsiella pneumonia.
10. The method of claim 7 , wherein disrupting ion transport comprises disrupting potassium ion transport.
11. The method of claim 1 , wherein the bacterial infection is caused by Clostridium.
12. The method of claim 1 , wherein the bacterial infection is caused by Staphylococcus.
13. The method of claim 1 , wherein the bacterial infection is caused by Enterococcus.
14. The method of claim 1 , wherein the bacterial infection is caused by C. difficile.
15. The method of claim 1 , wherein the bacterial infection is caused by S. aureus.
16. The method of claim 1 , wherein the bacterial infection is caused by methicillin-resistant S. aureus.
17. The method of claim 1 , wherein the bacterial infection is caused by vancomycin-resistant Enterococcus.
18. The method of claim 1 , wherein the bacterial infection is caused by P. aeruginosa.
19. The method of claim 1 , wherein the bacterial infection is caused by Kelbsiella pneumonia.