Multifunctional Radical Quenchers for Mitochondrial Dysfunction

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Solution Overview

Problem

Current treatments for mitochondrial disorders associated with decreased ATP production and oxidative stress, such as Friedreich's ataxia, Leber's Hereditary Optic Neuropathy, and Kearns-Sayre Syndrome, lack effective therapeutic agents that can mitigate mitochondrial dysfunction and oxidative damage.

Innovation Solution

Development of novel multifunctional radical quenching compounds, represented by formula (I), which are administered to treat or suppress diseases by reducing oxidative stress and enhancing mitochondrial function, thereby addressing diminished ATP production and lipid peroxidation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for mitochondrial disorders, then current standard care is maintained, but effective therapeutic agents to mitigate mitochondrial dysfunction and oxidative damage are lacking

Engineering Contradiction:
Improveeffectiveness of therapeutic agentsVSAvoidability to address multiple mitochondrial disorders
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by designing a class of compounds (formula I) that can treat multiple mitochondrial disorders through a common mechanism. The compounds serve multiple functions: they quench radicals, scavenge reactive oxygen species, and protect mitochondrial membranes, making them effective across different disease states including Friedreich's ataxia, Leber's Hereditary Optic Neuropathy, and other mitochondrial cytopathies.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent utilizes parameter changes by modifying molecular structures (changing R1-R6 substituents, n values, and X groups) to optimize the compounds' antioxidant and radical-quenching properties. These structural parameter variations allow the same basic compound class to effectively address different mitochondrial disorders with varying severity and specific pathologies.

Inventive Principle:
Principle #35Parameter changes

2Use of energy by moving object

If mitochondrial function is decreased leading to diminished ATP production, then energy deficiency occurs, but oxidative stress and lipid peroxidation increase causing further damage

Engineering Contradiction:
ImproveATP productionVSAvoidoxidative stress
Core Design Contradiction:
Use of energy by moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful oxidative stress and radical production into beneficial effects by using the compounds to quench radicals and scavenge reactive oxygen species. The same mitochondrial processes that produce ATP also generate radicals; the compounds harness this by providing radical-quenching mechanisms that protect against the harmful effects while preserving the useful energy production function.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The compounds act as intermediary agents between the mitochondrial electron transport chain and the cell's antioxidant defense systems. They mediate the interaction by directly interacting with radicals and reactive oxygen species generated during ATP production, transferring the burden of oxidative damage management from the cell's existing defense systems to the therapeutic compounds.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If radical quenching compounds are developed to treat mitochondrial disorders, then oxidative stress is reduced, but the compounds must be effective across multiple disease states and conditions

Engineering Contradiction:
Improveoxidative stressVSAvoidapplicability to multiple diseases
Core Design Contradiction:
Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent achieves universality by creating a broad class of radical quenching compounds that can address multiple disease states through a common mechanism. The compounds are designed to be effective across mitochondrial disorders, aging-related conditions, cancer, and other diseases with oxidative stress components, making them universally applicable therapeutic agents.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent employs parameter changes by systematically varying molecular parameters (substituents R1-R6, chain lengths, functional groups) to create a family of compounds with optimized properties for broad-spectrum efficacy. These parameter variations allow the same basic structure to effectively treat different diseases while maintaining consistent radical-quenching and antioxidant activities.

Inventive Principle:
Principle #35Parameter changes

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 protect mitochondria and cells from oxidative stress, slowing disease progression and improving energy production in mitochondrial disorders, including Friedreich's ataxia, Leber's Hereditary Optic Neuropathy, and other conditions like obesity, cancer, and Alzheimer's Disease.

Implementation Method 1

Multifunctional radical quenchers for the treatment of mitochondrial dysfunction

Methodology Applied
Scientific EffectRadical quenching:

Implementation Method 2

reducing oxidative stress and enhancing mitochondrial function

Methodology Applied
Scientific EffectOxidative stress reduction: Oxidation

Implementation Method 3

diminished ATP production and/or oxidative stress and/or lipid peroxidation

Methodology Applied
Scientific EffectLipid peroxidation inhibition: Oxidation

Data Source

PatentUS9334250B2Multifunctional radical quenchers for the treatment of mitochondrial dysfunction
Publication Date: 2016.05.10 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA

AI summary

The present disclosure provides compounds of formula (I):compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with decreased mitochondrial function resulting in diminished ATP production and/or oxidative stress and/or lipid peroxidation.