Novel Antibiotic Compound with 8-Membered Ring for Resistant Bacteria

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Solution Overview

Problem

The emergence of antibiotic-resistant bacteria, such as MRSA and ESBL-producing Enterobacteriaceae, poses a significant threat due to the limited effectiveness of current antibiotics, necessitating the development of novel antibiotics effective against resistant strains.

Innovation Solution

A novel cyclic compound with an unprecedented (E)-1,4-dioxo-but-2-ene moiety in an 8-membered ring structure, potentially substituted with halogen or alkyl groups, exhibiting antibacterial activity specifically against Gram-positive bacteria like MRSA and Streptococcus species, while being inactive against Gram-negative bacteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing antibiotics are used to treat bacterial infections, then treatment of common bacterial infections is effective, but treatment of infections caused by antibiotic-resistant bacteria fails

Engineering Contradiction:
Improveeffectiveness against antibiotic-resistant bacteriaVSAvoidbroad-spectrum coverage
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by designing the compound to have selective activity against Gram-positive bacteria while being inactive against Gram-negative bacteria. This is achieved through the specific molecular structure with the (E)-1,4-dioxo-but-2-ene moiety in an 8-membered ring, which creates specific interactions with Gram-positive bacterial targets while avoiding Gram-negative targets, thus providing targeted effectiveness against resistant strains without requiring broad-spectrum coverage

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by modifying the chemical structure parameters of antibiotic compounds. The novel compound features specific structural parameters including the (E)-1,4-dioxo-but-2-ene moiety, 8-membered ring structure, and specific substituent patterns that differentiate it from existing antibiotics. These structural parameter changes enable the compound to overcome resistance mechanisms that have evolved against conventional antibiotics

Inventive Principle:
Principle #35Parameter changes

2Reliability

If novel antibiotic compounds are developed to combat resistant bacteria, then effectiveness against resistant strains improves, but development complexity and time increase

Engineering Contradiction:
Improveantibacterial activity against resistant strainsVSAvoidmolecular structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the molecular structure into distinct functional segments: the core 8-membered ring structure containing the (E)-1,4-dioxo-but-2-ene moiety, and variable substituent groups at specific positions. This segmentation allows for systematic optimization of antibacterial activity against resistant strains while managing molecular complexity through modular design, where the core structure provides the essential activity and substituents fine-tune the properties

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses parameter changes by systematically varying specific structural parameters of the novel compound, including the presence and position of halogen or alkyl substituents on the 8-membered ring. These controlled parameter changes enable optimization of antibacterial activity against resistant strains while maintaining manageable molecular complexity through defined structural constraints

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3174867B1Novel antibiotic
Publication Date: 2019.11.27 KONINK NEDERLANDSE AKADE VAN WETENSCHAPPEN
  • EP3174867B1 patent drawingFigure 1
  • EP3174867B1 patent drawingFigure 2
  • EP3174867B1 patent drawingFigure 3

AI summary

The present invention relates to novel compounds, comprising an 8-or 9- membered cyclic structure, wherein an (E)-1,4-dioxo-but-2-ene moiety is embedded in said cyclic structure and to pharmaceutical compositions comprising these compounds. The compounds may be used as medicaments, in particular as medicaments for treating and preventing microbial infections, such as infections by multidrug resistant and/or Gram-positive bacteria. The invention further relates to fermentation processes wherein fungi of the genus Ulocladium are used for producing the novel compounds.