Cystobactamides Target Resistant Gram-Negative Bacteria

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Solution Overview

Problem

Current antibiotics are ineffective against certain Gram-negative bacteria, such as E. coli, P. aeruginosa, and A. baumannii, due to their resistance and broad-spectrum antibiotic misuse, leading to a need for new antimicrobial agents with broad-spectrum activity.

Innovation Solution

Development of Cystobactamides, novel natural products isolated from Myxobacterium Cystobacter velatus, which exhibit strong antibiotic activity against Gram-negative and Gram-positive bacteria, including compounds of specific structural formulas and their pharmaceutically acceptable salts, solvates, or hydrates, for use in treating bacterial infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If broad-spectrum antibiotics are used to treat bacterial infections, then the treatment coverage is improved, but bacterial resistance develops more rapidly

Engineering Contradiction:
Improvetreatment coverageVSAvoidbacterial resistance
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by designing cystobactamides with specific molecular structures (beta-lactam core with distinct R1-R6 substituents) that enable selective binding to bacterial penicillin-binding proteins. This structural specificity allows the antibiotic to target bacterial cells precisely while sparing human cells, achieving broad-spectrum activity against both Gram-positive and Gram-negative bacteria without promoting cross-resistance to other antibiotic classes

Inventive Principle:
Principle #3Local quality

2Reliability

If new antibiotics are developed to overcome resistance, then the effectiveness against resistant strains is improved, but the complexity of drug development increases

Engineering Contradiction:
Improveeffectiveness against resistant strainsVSAvoiddrug development complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs parameter changes by systematically modifying the chemical structure of cystobactamides through varying substituents at positions R1 through R6. These structural parameters are optimized to enhance activity against resistant bacterial strains while maintaining stability against beta-lactamases. The defined stereochemistry at specific carbon positions further fine-tunes the molecule's interaction with bacterial targets, achieving improved effectiveness without requiring entirely new chemical scaffolds

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3224238B1Novel cystobactamides
Publication Date: 2021.08.11 HELMHOLTZ ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH
  • EP3224238B1 patent drawingFigure 1
  • EP3224238B1 patent drawingFigure 2
  • EP3224238B1 patent drawing

AI summary

The present invention provides cystobactamides of formula (I) and the use thereof the treatment or prophylaxis of bacterial infections.