MRSA biofilm inhibition
Provided is a darwinolide compound having a previously undescribed carbon skeleton and the crystalline form thereof. Also provided are processes of isolating darwinolide, compositions comprising darwinolide, and methods of treating infection, such as a methicillin-resistant Staphylococcus aureus biofilm infection.
1. A method of treating infection in a subject in need thereof, the method comprising administering to the subject an effective amount of darwinolide compound having a formula of
wherein the infection is a bacterial infection.
2. The method of claim 1 , wherein the bacterial infection is caused by MRSA.
3. The method of claim 1 , wherein the bacterial infection is caused by bacteria that form a bacterial biofilm.
4. The method of claim 3 , wherein the bacterial biofilm is a MRSA bacterial biofilm.
5. The method of claim 1 , wherein the bacterial infection is resistant to treatment with one or more antibiotics.
6. The method of claim 3 , wherein the darwinolide compound inhibits bacterial biofilm formation.
7. The method of claim 1 , wherein the darwinolide compound is combined with a pharmaceutically acceptable carrier.
8. The method of claim 7 , wherein the darwinolide compound and pharmaceutically acceptable carrier is administered orally, intravenously, trans-dermally, or topically.
9. The method of claim 8 , wherein the darwinolide compound and pharmaceutically acceptable carrier is administered topically.
10. The method of claim 9 , wherein the darwinolide compound and pharmaceutically acceptable carrier is administered topically to an area of the skin and/or mucous membrane infected by MRSA.
11. A crystalline form of darwinolide compound having a formula of
wherein the crystalline compound demonstrates X-ray diffraction data: space group P2 1 2 1 2 1 , a 7.6629(6) A, b 9.5182(8) A, c 27.012(2) A.
12. A process of isolating darwinolide compound, comprising the steps of:
(a) contacting a source of the darwinolide compound with an organic solvent to obtain a lipophilic extract;
(b) isolating the darwinolide compound from the lipophilic extract of step (a) using high-performance liquid chromatography; and
(c) optionally crystallizing the darwinolide compound obtained in step (b), wherein the darwinolide compound has a formula of 0
13. The process of claim 12 , wherein the organic solvent in step (a) is selected from the group consisting of methanol, ethanol, dichloromethane, chloroform, and combinations thereof.
14. The process of claim 12 , wherein the organic solvent in step (a) is dichloromethane.
15. The process of claim 12 , wherein the high-performance liquid chromatography of step (b) comprises eluting the darwinolide compound using a solvent system comprising acetonitrile.
16. The process of claim 15 , wherein the solvent system comprises a gradient from 60% acetonitrile in water to 100% acetonitrile.
17. The process of claim 12 , wherein the source of the darwinolide compound is Dendrilla membranosa.
18. A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and an effective amount of darwinolide compound having a formula of