Small molecule RNase inhibitors and methods of use
Small molecule inhibitors of bacterial ribonuclease (e.g., RnpA) and methods for their synthesis and use are described herein. The methods of using the compounds include treating and preventing microbial infections and inhibiting bacterial ribonuclease.
1. A method of treating, reducing, or inhibiting a bacterial infection in a subject, comprising administering to the subject an effective amount of an RNase inhibitor of the following structure:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein the bacterial infection is a Staphylococcus infection.
2. The method of claim 1 , wherein the Staphylococcus infection is a Staphylococcus aureus infection.
3. The method of claim 2 , wherein the Staphylococcus aureus infection is a drug-resistant Staphylococcus aureus infection.
4. The method of claim 2 , wherein the Staphylococcus aureus infection is a biofilm-associated Staphylococcus aureus infection.
5. The method of claim 1 , wherein the RNase inhibitor is a RnpA inhibitor.
6. The method of claim 1 , further comprising administering a second compound, wherein the second compound is an antibacterial compound.
7. A method of inhibiting a bacterial ribonuclease comprising contacting the bacterial ribonuclease with an effective amount of an RNase inhibitor of the following structure:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein the bacterial ribonuclease is Staphylococcus aureus RNase P.
8. The method of claim 7 , wherein the bacterial ribonuclease is RnpA.
9. The method of claim 7 , wherein the contacting occurs in vivo.
10. The method of claim 7 , wherein the contacting occurs in vitro.