Antimicrobial compounds, compositions and methods of use thereof
Described herein are antimicrobial compounds identified via a high-throughput screen to identify compounds that produce anucleate cells in E. coli after cell division occurs. Compound 1 (5-nonyloxytryptamine) and its analogs are small molecule inhibitors of the nucleoid occlusion system and/or proteins that are responsible for maintaining the structure of the chromosome. The antimicrobial compounds are useful to treat bacterial infections as well as to inhibit bacterial growth.
1. A method of treating a subject in need of treatment for a bacterial infection comprising administering to the subject a compound of Formula III or IV, or a pharmaceutically acceptable salt thereof,
wherein R is a substituted or unsubstituted C 5 -C 18 alkyl group, a substituted or unsubstituted C 5 -C 18 alkenyl group, a substituted or unsubstituted C 5 -C 18 alkynyl group, a substituted or unsubstituted C 5 -C 18 cycloalkyl group, a substituted or unsubstituted C 6 -C 18 cycloalkenyl group, or a substituted or unsubstituted C 8 -C 18 cycloalkynyl group.
2. The method of claim 1 , wherein, R is a substituted or unsubstituted C 5 -C 18 alkyl group.
3. The method of claim 2 , wherein R is substituted with one or more C 1 -C 20 alkyl groups, C 6 -C 20 aryl, and/or C 7 -C 13 arylalkyl groups.
4. The method of claim 2 , wherein R is substituted with one or more C 1 -C 4 alkyl groups or a C 6 -C 10 aryl group.
5. The method of claim 1 , wherein the compound is
6. The method of claim 1 , wherein the bacteria causing the infection are Gram-negative bacteria, Gram-positive bacteria, or bacteria that are neither Gram-positive nor Gram-negative.
7. The method of claim 6 , wherein the Gram-negative bacteria is Escherichia coli, Pseudomonas aeruginosa, Candidatus liberibacter, Agrobacterium tumefaciens, Branhamella catarrhalis, Citrobacter di versus, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Salmonella typhimurium, Neisseria meningitidis, Serratia marcescens, Shigella sonnei, Shigella boydii, Neisseria gonorrhoeae, Acinetobacter baumannii, Salmonella enteriditis, Fusobacterium nucleatum, Veillonella parvula, Bacteroides forsythus, Actinobacillus actinomycetemcomitans, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Helicobacter pylori, Francisella tularensis, Yersinia pestis, Vibrio cholera, Shigella boydii, Morganella morganii, Edwardsiella tarda, Campylobacter jejuni , or Haemophilus influenzae.
8. The method of claim 6 , wherein the Gram-positive bacteria is a species of Bacillus, Listeria, Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Propionibacterium or Clostridium.
9. The method of claim 8 , wherein the Gram-positive bacteria is Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, Enterococcus faecalis, Streptococcus pyogenes, Bacillus cereus , or Bacillus anthracis.
10. The method of claim 9 , wherein the bacteria are carbapenam-resistant bacteria, methicillin-resistant Staphylococcus aureus , vanccomycin-resistant Enterococci or multi-drug resistant Neisseria gonorrhoeae.
11. The method of claim 1 , wherein the subject is a mammal.
12. The method of claim 11 , wherein the mammal is a human.
13. The method of claim 1 , wherein administration is topical administration.
14. The method of claim 1 , wherein administration is systemic administration.
15. A method of inhibiting bacterial growth comprising contacting bacteria with an antimicrobially effective amount of a compound of Formula III or IV, or a pharmaceutically acceptable salt thereof,
wherein R is a substituted or unsubstituted C 5 -C 18 alkyl group, a substituted or unsubstituted C 5 -C 18 alkenyl group, a substituted or unsubstituted C 5 -C 18 alkynyl groups substituted or unsubstituted C 5 -C 18 cycloalkyl group, a substituted or unsubstituted C 6 -C 18 cycloalkenyl group, or a substituted or unsubstituted C 8 -C 18 cycloalkynyl group.
16. The method of claim 15 , wherein the compound is
17. The method of claim 15 , wherein the bacteria are actively growing or are in the stationary phase.
18. The method of claim 15 , wherein the bacteria are in the form of a biofilm.