Boronated Compounds for Oxidative Stress Treatment

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

There is a strong need in the pharmaceutical chemistry field for new therapeutic boron compounds that do not have the drawbacks of existing compounds, such as toxicity and dosage limitations, particularly for treating neurodegenerative, cardiovascular diseases, and diabetes related to oxidative stress.

Innovation Solution

The development of structurally unique boronated compounds with improved neuroprotective and antiplatelet activities, which also inhibit enzymes involved in catecholamine metabolism and possess superior antioxidant and antiplatelet properties compared to lipoic acid, while ensuring better solubility and gastrointestinal absorption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing boron compounds are used for treating oxidative stress-related diseases, then therapeutic effect is achieved, but toxicity and dosage limitations occur

Engineering Contradiction:
Improvetherapeutic effectVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of boron compounds by changing parameters such as the boron-containing group (boronic acid, boronate ester), the linker chain length and saturation, and the terminal functional groups (hydroxyl, carboxyl, amine). These parameter changes result in compounds with improved therapeutic profiles that maintain efficacy while reducing toxicity and dosage limitations compared to existing boron compounds.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures combining a boron-containing group, a linker chain with specific properties (saturated or unsaturated, 1-10 carbons), and terminal functional groups. This composite approach allows optimization of multiple properties simultaneously - the boron group provides therapeutic activity while the linker and terminal groups modulate solubility, bioavailability, and reduce toxicity.

Inventive Principle:
Principle #40Composite materials

2Reliability

If lipoic acid is used as antioxidant, then ROS and RNS scavenging activity is achieved, but limited solubility and gastrointestinal absorption occur

Engineering Contradiction:
Improveantioxidant activityVSAvoidsolubility and absorption
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent systematically varies the linker chain parameters (length, saturation, cyclic vs linear) and terminal functional groups to optimize the balance between antioxidant activity and bioavailability. The linker chain can be saturated or unsaturated with 1-10 carbon atoms, and terminal groups include hydroxyl, carboxyl, and amine functionalities, allowing fine-tuning of solubility and gastrointestinal absorption while maintaining ROS and RNS scavenging capability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If boron compounds are designed with enhanced neuroprotective and antiplatelet activities, then disease treatment efficacy is improved, but molecular complexity increases

Engineering Contradiction:
Improveneuroprotective and antiplatelet activityVSAvoidmolecular structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the boron compound into distinct functional segments: a boron-containing group (providing neuroprotective and antiplatelet activity), a linker chain (providing structural flexibility and solubility), and terminal functional groups (modulating bioavailability). This segmentation allows each component to be optimized independently for its specific function while maintaining overall molecular simplicity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent designs a universal molecular platform where the core boron-containing structure with a modifiable linker and terminal groups can provide multiple therapeutic activities simultaneously - neuroprotective effects, antiplatelet activity, and antioxidant properties - through a single compound design, reducing the need for multiple separate agents.

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

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

These compounds effectively treat neurodegenerative and cardiovascular diseases by reducing cell death, inhibiting enzyme degradation, and preventing oxidative stress without toxicity, offering improved dosing flexibility and enhanced bioavailability.

Implementation Method 1

Lipoic acid acts as a cofactor for several mitochondrial enzymes. Both oxidized (LA) and reduced (DHLA) forms contributes to the antioxidant properties of the molecule. Lipoic acid is a powerful antioxidant since it is a direct scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are produced following oxidative stress

Methodology Applied
Scientific EffectRadical scavenging: Oxidation

Implementation Method 2

Lipoic acid regulates the homeostasis of metals by chelating copper (II), iron (II), and zinc (II) by generating stable complexes

Methodology Applied
Scientific EffectChelation: Chemical Bonding

Implementation Method 3

Lipoic acid is a natural product, soluble both in water and lipids, able to easily cross cellular membrane and blood brain barrier

Methodology Applied
Scientific EffectPassive diffusion: Diffusion

Data Source

PatentEP3495372B1Boronated derivatives for the treatment of diseases and conditions associated to oxidative stress
Publication Date: 2021.04.07 UNIV DEGLI STUDI DELLAQUILA
  • EP3495372B1 patent drawingFigure 1
  • EP3495372B1 patent drawingFigure 2
  • EP3495372B1 patent drawingFigure 3

AI summary

The present invention is related to boronated compounds with neuroprotective, antiplatelet, antitumor, and antimicrobial activities for the treatment of diseases and conditions associated to oxidative stress.