Targeting Oral Biofilms with 2-Aminoimidazole/Triazole Conjugates
DESCRIPTION (provided by applicant): Dental caries, or tooth decay, affects hundreds of millions of people each year, and is second only to the common cold in its prevalence world-wide. New therapeutics to aid in the prevention of dental caries would repr
esent a significant advancement in oral health care. Caries is caused by acid-producing bacteria in the presence of carbohydrates, and these bacteria are particularly difficult to eradicate due to their ability to form biofilms, or plaque. While tooth br
ushing and biocide-containing mouthwash have reduced the occurrence of and severity of dental caries, these treatments cannot completely eradicate biofilms of the undesired bacteria, and so dental caries remains a significant medical problem. An ideal trea
tment for dental caries would be the selective elimination of pathogenic bacteria from plaque. Dr. Christian Melander's Research Group at North Carolina State University has developed non-toxic molecules that are active toward selectively inhibiting and di
spersing bacterial biofilms. In this proposal, Agile Sciences will collaborate with the Melander Group to synthesize analogues of 2-aminoamidizole triazole (2-AIT) molecules developed in the Melander Lab and then to screen these compounds to identify those
that selectively inhibit Streptococcus mutans biofilms. S. mutans has been strongly associated with the etiology of dental caries, and the formation of tenacious biofilm by S. mutans is a key virulent determinant in the disease process. Furthermore, the p
roposed work aims to identify molecules that inhibit and disperse S. mutans while not affecting the biofilm formation by oral commensal bacteria, S. sanguinis and S. gordonii. Based on Agile Sciences and the Melander Group's previous success and substanti
al experience in 1) tuning molecules to selectively inhibit and disperse biofilms, and 2) analogue synthesis utilizing a variety of synthetic and combinatorial techniques, it is anticipated that a large number of compounds with high probability of showing
selective activity toward S. mutans biofilms will be screened over the time-frame of this Phase I STTR study. The specific aims of this proposal are: Specific Aim #1: Synthesize a diverse library of 2-AIT derivatives. Specific Aim #2: Assay 2-AIT derivat
ives for anti-biofilm activity using high-throughput screening under static conditions. Specific Aim #3: Examine the effects of 2-AIT derivatives on biofilm formation using a flow-cell system under shear force conditions. Specific Aim #4: To screen lead
Compounds for toxicity. PUBLIC HEALTH RELEVANCE: The proposed study aims to develop a novel approach for treating dental caries, or tooth decay. Dental caries is caused by an elevated ratio of pathogenic to beneficial bacteria in the oral cavity.
This work describes the development of molecules that may selectively release the pathogenic bacteria from plaque while not affecting the beneficial bacteria.
Small Business Information at Submission:
Principal Investigator:Eva Garland
AGILE SCIENCES, INC.
AGILE SCIENCES, INC. 3309 MILTON RD RALEIGH, NC 27609
Number of Employees: