Modified Mannose Compounds Inhibit E. coli Adhesion
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Solution Overview
Problem
Current treatments for inflammatory bowel diseases (IBD) and urinary tract infections (UTI) do not effectively target the specific bacterial adhesion mechanisms, particularly the interaction between E. coli and host cells, leading to sub-mucosal infections and inflammation.
Innovation Solution
Development of compounds with modified mannose moieties that inhibit the adhesion of E. coli by blocking the interaction between type 1 pili and CEACAM6, represented by specific structural formulas, which are more stable and effective than unmodified mannose moieties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If unmodified mannose moieties are used to inhibit bacterial adhesion, then the compounds can block the interaction between type 1 pili and CEACAM6, but the stability of the compounds is insufficient leading to reduced therapeutic effectiveness
Solution Approach 1:
The patent modifies the mannose moiety structure by changing chemical parameters - specifically replacing the natural mannose structure with modified versions where hydroxyl groups are substituted with various functional groups (e.g., -CH2OH, -OCH3, -F, -Cl, -Br, -I, -CF3, -OCF3, -OCHF2, -OCH2F, -OCH2Cl, -OCH2Br, -OCH2I). These parameter changes in molecular structure enhance the stability of the compounds while maintaining their ability to inhibit bacterial adhesion to CEACAM6 receptors.
2Object-affected harmful factors
If current treatments are used for IBD and UTI, then general anti-inflammatory effects are achieved, but the specific bacterial adhesion mechanisms are not effectively targeted
Solution Approach 1:
The modified mannose compounds act as intermediary molecules that specifically bind to CEACAM6 receptors on host cells, blocking the interaction between bacterial type 1 pili (FimH adhesins) and the receptor. This intermediary action provides targeted inhibition of bacterial adhesion without requiring broad-spectrum anti-inflammatory effects, thereby achieving treatment specificity while remaining manufacturable through standard organic synthesis methods.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds effectively prevent the adhesion and intracellular replication of adherent-invasive E. coli, reducing the establishment of sub-mucosal infections and inflammation in IBD and UTI, thereby providing a novel therapeutic approach for these conditions.
Implementation Method 1
the binding of adhesins expressed on the bacterial cell surface to defined glycosylated receptors on the host tissue surface is considered to be an initial and critical step in pathogenesis
Data Source
AI summary
The present invention relates to compounds useful for the treatment or prevention of bacteria infections. These compounds have formula (I) The invention also provides processes for making the compounds described herein. Furthermore, the present invention provides a composition comprising the compounds described herein, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The present invention also provides methods of treating or preventing bacteria infection in a subject, comprising administering to the subject an effective amount of the compound or the composition described herein.