10H-benzo[g]pteridine-2,4-dione derivatives for microbial inactivation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current photosensitizers for photodynamic inactivation of microorganisms, such as 10-methyl-10H-benzo[g]pteridine-2,4-dione derivatives, have low affinity for microorganisms and insufficient inactivation due to short diffusion distance of singlet oxygen, leading to treatment challenges with resistant pathogens, especially in immunocompromised patients.

Innovation Solution

Development of a 10H-benzo[g]pteridine-2,4-dione derivative with a specific chemical structure that enhances singlet oxygen yield and affinity for microorganisms, allowing for effective photodynamic therapy by binding to microorganisms and generating reactive oxygen species upon irradiation, thereby inactivating them.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If 10-methyl-10H-benzo[g]pteridine-2,4-dione derivatives are used as photosensitizers, then singlet oxygen yield is high, but affinity for microorganisms is low

Engineering Contradiction:
Improvesinglet oxygen yieldVSAvoidaffinity for microorganisms
Core Design Contradiction:
Use of energy by moving objectVSReliability

Solution Approach 1:

The patent modifies the chemical structure of 10H-benzo[g]pteridine-2,4-dione derivatives by introducing specific substituents at defined positions (where at least one of R1-R6 is -NRbRc and at least one of R7-R12 is -Y or -CH2Y) to optimize both singlet oxygen quantum yield and microbial affinity simultaneously

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite molecular structures combining the pteridine-dione core with specific functional groups (amino, alkylamino, arylamino groups) to achieve synergistic effects that enhance both photosensitizing capability and microbial binding affinity

Inventive Principle:
Principle #40Composite materials

2Reliability

If singlet oxygen is generated for photodynamic inactivation, then microorganisms can be inactivated, but diffusion distance is short leading to insufficient inactivation

Engineering Contradiction:
Improvemicroorganism inactivationVSAvoiddiffusion distance of singlet oxygen
Core Design Contradiction:
ReliabilityVSLength of moving object

Solution Approach 1:

The patent applies preliminary action by having the photosensitizer bind to microorganisms before light irradiation, ensuring the photosensitizer is already positioned at the target site where singlet oxygen will be generated, thereby compensating for the short diffusion distance

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses the microorganism surface and internal structures as an intermediary medium to deliver the photosensitizer directly to the target, allowing singlet oxygen to be generated in close proximity to critical microbial components without requiring long-distance diffusion

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If traditional antimicrobials are used, then pathogen treatment is possible, but resistant pathogens emerge

Engineering Contradiction:
Improvepathogen treatmentVSAvoidresistance development
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent replaces the chemical mechanism of traditional antimicrobials (which target specific metabolic pathways) with a photophysical mechanism (light activation generating reactive oxygen species), thereby eliminating the selective pressure that drives resistance development while maintaining effective pathogen inactivation

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 derivative achieves high log 10 reduction factors, reducing microorganisms by 99.9% or more, effectively inactivating viruses, bacteria, and fungi, offering a promising alternative to traditional antimicrobials with reduced resistance risks.

Implementation Method 1

Two different photooxidative processes play a crucial role in the photodynamic inactivation of microorganisms. The excited photosensitizer can cause the formation of reactive oxygen species (ROS), whereby on the one hand radicals, for example superoxide anions, hydrogen peroxide or hydroxyl radicals, and/or on the other hand, excited molecular oxygen, for example singlet oxygen, can be formed.

Methodology Applied
Scientific EffectPhotooxidation: Photo-oxidation

Implementation Method 2

Photodynamic inactivation of microorganisms has proven to be an alternative method. The prerequisite for photooxidative inactivation to occur is, on the one hand, the presence of a sufficient amount of oxygen and, on the other hand, the localization of a so-called photosensitizer, which is excited by light of a corresponding wavelength.

Methodology Applied
Scientific EffectPhotodynamic inactivation:

Implementation Method 3

The excited photosensitizer can cause the formation of reactive oxygen species (ROS), whereby on the one hand radicals, for example superoxide anions, hydrogen peroxide or hydroxyl radicals, and/or on the other hand, excited molecular oxygen, for example singlet oxygen, can be formed.

Methodology Applied
Scientific EffectEnergy transfer:

Data Source

PatentEP3586632B110h-benzo[g]pteridine-2,4-dione derivatives, method for producing same and use of same
Publication Date: 2022.09.28 TRIOPTOTEC GMBH
  • EP3586632B1 patent drawingFigure 1~1a
  • EP3586632B1 patent drawingFigure 1b
  • EP3586632B1 patent drawingFigure 2~2a

AI summary

The present invention relates to 10H-benzo[g]pteridine-2,4-dione derivatives for use as photosensitizers in the photodynamic inactivation of microorganisms and a pharmaceutical composition containing the same.