Anti-inflammatory and quorum sensing inhibition compounds and methods of making and using them
The invention provides novel compositions based on a structure designated as “Honaucin A”, including Honaucin A variants and analogs, and pharmaceutical compositions, liposomes and nanoparticles comprising them, and methods of making and using them. In one embodiment, these Honaucin A compounds, and variants and analogs thereof are used to ameliorate (including to treat or prevent) inflammation. In one embodiment, these Honaucin A compounds, and variants and analogs thereof are used to ameliorate (including to treat or prevent) inflammation. In one embodiment, these Honaucin A compounds, and variants and analogs thereof are used as bacterial quorumsensing inhibitors. Accordingly, in alternative embodiments the compositions of the invention are used as anti-bacterial agents.
1. A method for treating or ameliorating an infection or trauma, or disease or condition associated with inflammation, infection or trauma, comprising administering to an individual in need thereof a compound
(a) having a formula selected from the group consisting of:
(b) derivatives or analogs of the compounds of (a) comprising variations of saturation level and halogenation of the 4-chloro crotonic acid functional group.
2. The method of claim 1 , wherein the disease or condition treated or ameliorated comprises an inflammatory component.
3. The method of claim 1 , wherein:
(a) the derivatives or analogs optionally comprise variations of chain length or chain saturation comprising alkene or alkyne moieties;
(b) the variations of chain length or chain saturation comprise a chain moiety —COO—(C n )—Cl, where the integer n can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or more;
(c) the derivatives or analogs comprise variations of halogenation, or a substitution of a bromine, an iodine, an astatine, or a fluorine for the chlorine group;
(d) the compound is a polyhalogenated compound, or a polyhalogenated compound further comprising a second or third or an additional halogen moiety; or
(e) the ring and/or chain are substituted with a hydrogen, halo, hydroxy (—OH), phenoxy, thiol (—SH), cyano (—CN), formyl (—CHO), alkyl, haloalkyl, alkene, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, substituted aryl, amino, nitro (—NO 2 ), alkoxy, haloalkoxy, thioalkoxy, alkanoyl, haloalkanoyl and/or carbonyloxy group.
4. The method of claim 1 , wherein any one, several or all of the hydrogen groups are independently substituted with a fluorine or a deuterium.
5. The method of claim 1 , wherein the derivatives or analogs comprise have a six membered ring with or without an oxygen, or a phenolic ring.
6. The method of claim 1 , one, several or all of the oxygen groups are independently substituted with a sulfur moiety.
7. The method of claim 1 , wherein the compound is formulated as a pharmaceutical composition.
8. The method of claim 1 , wherein the compound is formulated as a liposome.
9. The method of claim 1 , wherein the compound is formulated as a nanoparticle.
10. The method of claim 1 , wherein the administered compound has the formula:
11. The method of claim 10 , wherein the administered compound is Honaucin A.
12. The method of claim 1 , wherein the method comprises treating or ameliorating an infection.
13. The method of claim 1 , wherein the method comprises treating or ameliorating a trauma.
14. The method of claim 1 , wherein the method comprises treating or ameliorating a disease or condition associated with inflammation.
15. The method of claim 1 , wherein the method comprises treating or ameliorating a disease or condition associated with a trauma.
16. The method of claim 1 , wherein the method comprises treating or ameliorating an autoimmune disease.
17. The method of claim 1 , wherein the method comprises treating or ameliorating inflammation caused by a surgical trauma.