Methods and compositions for treating bacterial infection
The present disclosure relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present disclosure provides compounds as therapeutic agents against bacterial infections (e.g., biofilms). The present disclosure also provides compounds as therapeutic agents in methods for treating pneumonia, methods for reducing bacterial virulence, methods for treating a bacterial wound infection, and methods for treating a urinary tract infection. The present disclosure also provides methods for treating a bacterial infection, wherein the bacterial infection has or is suspected of having an antibiotic-resistant bacteria. The present disclosure also provides surfaces coated with the chemical compounds disclosed herein.
1. A composition comprising: a compound having the structure of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a C1 alkyl.
2. The composition of claim 1 , wherein the compound is selected from the group consisting of:
and combinations thereof.
3. A method for treating pneumonia in a subject in need thereof, the method comprising: administering a composition comprising a compound of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is H, C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a Cl alkyl.
4. The method of claim 3 , wherein the compound is selected from the group consisting of
and combinations thereof.
5. The method of claim 3 , further comprising administering an antibiotic.
6. A method for reducing bacterial virulence in a subject in need thereof, the method comprising: administering a composition comprising a compound of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is H, C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a Cl alkyl.
7. The method of claim 6 , wherein the compound is selected from the group consisting of
and combinations thereof.
8. The method of claim 6 , further comprising administering an antibiotic.
9. A method for treating a bacterial wound infection in a subject in need thereof, the method comprising: administering a composition comprising a compound of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is H, C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a Cl alkyl.
10. The method of claim 9 , wherein the compound is selected from the group consisting of
and combinations thereof.
11. The method of claim 9 , further comprising administering an antibiotic.
12. A method for treating a urinary tract infection in a subject in need thereof, the method comprising: administering a composition comprising a compound of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is H, C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a Cl alkyl.
13. The method of claim 12 , wherein the compound is selected from the group consisting of
and combinations thereof.
14. The method of claim 12 , further comprising administering an antibiotic.
15. A method for treating a bacterial infection, wherein the bacterial infection has or is suspected of having an antibiotic-resistant bacteria, the method comprising:
administering a composition comprising a compound of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is H, C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a Cl alkyl; and
administering an antibiotic, wherein the antibiotic-resistant bacteria is resistant to the antibiotic.
16. The method of claim 15 , wherein the compound is selected from the group consisting of
and combinations thereof.
17. A surface coated with a composition comprising a compound of Formula V
wherein X is SR 1 , NH 2 , NHR 1 , NR 1 R, OH, OR 1 , or Cl; wherein R, R 1 and R 2 are, independently, H, a C1-C8 alkyl or alkenyl or cycloalkyl, optionally substituted with F, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl or heteroaryl, wherein one or more alkyl carbons may be replaced by O; R 3 and R 4 are, independently, a C1-C8 alkyl; R 5 is H, C1-C6 alkyl, CN, OR 6 , NR 6 2 , COR 6 , CO 2 R 6 , CONHR 6 , aryl, heteroaryl, SO 2 R 6 , NHCOR 6 , SO 2 NHR 6 , or OCOR 6 ; R 6 is H, C1-C6 alkyl, C0-C3 alkyl-aryl, or C0-C3 alkyl-heteroaryl, all optionally substituted; and R 11 is H or a Cl alkyl.
18. The surface of claim 17 , wherein the compound is selected from the group consisting of
and combinations thereof.
19. The surface of claim 17 , wherein the surface is a surface of a medical device.