Efficacy in treating bacterial infections
View Patent ↗The present disclosure relates to molecules which function as selective modulators (i.e., inhibitors and agonists) of the Ras-homologous (Rho) family of small GTPases and, in particular, CDC42 GTPase, and their use to treat bacterial infection including systemic infection from sources such as Staphylococcus aureus.
1. A method of suppressing bacterial infection comprising:
administering ML 141 or its analogs to a patient with Staphylococcus infection,
where the analogs are defined by the following structure:
where R 1 is selected from the group consisting of: hydrogen, hydroxyl, halogen, methoxy, methylenedioxy (—O—CH 2 —O—), wherein one oxygen of the methylenedioxy (—O—CH 2 —O—) is bonded to a carbon on a phenyl ring and the other oxygen of the methylenedioxy (—O—CH 2 —O—) is bonded to an adjacent carbon on the phenyl ring, and polyethylene glycol (—(O—CH 2 —CH 2 ) n —O-Me) wherein n is any integer;
where R 2 is selected from the group consisting of: hydrogen, methoxy, and polyethylene glycol (—(O—CH 2 —CH 2 ) n —O-Me) wherein n is any integer;
where R 3 is selected from the group consisting of: hydrogen and methyl.
2. The method of claim 1 wherein said Staphylococcus infection is from Staphylococcus aureus.
3. The method of claim 1 wherein administering includes providing ML 141 or its analogs adjacent to cells of the patient.
4. The method of claim 1 wherein administering includes testing ML 141 on cells of the patient.
5. The method of claim 1 wherein administering includes testing at least one analog on cells of the patient.
6. The method of claim 1 wherein suppressing bacterial infection includes suppressing initial bacterial infection.
7. The method of claim 1 wherein suppressing bacterial infection includes suppressing persistent bacterial infection.
8. The method of claim 7 wherein administering includes providing approximately 1 μM of ML 141.
9. The method of claim 7 wherein administering includes providing approximately 10 μM of ML 141 or its analogs.
10. The method of claim 1 wherein the patient is an animal patient.
11. The method of claim 1 wherein the patient is a human patient.
12. The method of claim 1 wherein cells of the patient include CDC42.
13. The method of claim 1 , wherein R 1 is selected from the group consisting of methoxy, polyethylene glycol (—(O—CH 2 —CH 2 ) n —O-Me), and methylenedioxy (—O—CH 2 —O—), where n is any integer.
14. The method of claim 1 , where R 1 is a halogen.
15. The method of claim 14 , wherein the halogen is chloride.
16. The method of claim 15 , wherein ML 141 or its analogs are present in a pharmaceutically accepted solvent or delivery vehicle selected from the group consisting of polyethylene glycol (PEG), dimethyl sulfoxide, ethanol, and combinations thereof.
17. The method of claim 16 , wherein the solvent or delivery vehicle is polyethylene glycol.
18. A method of suppressing bacterial infection comprising:
administering ML 141 or its analogs to a patient infected by bacteria of the genus Staphylococcus,
where the analogs are defined by the following structures: