Novel Cyclic Peptide Antibiotics for Polymyxin-Resistant Bacteria

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Solution Overview

Problem

The emergence of multi-drug resistant bacteria and fungi poses a significant threat, with limited effective treatments, particularly for polymyxin-resistant bacteria and fungal infections, and existing antibiotics like polymyxins are nephrotoxic, necessitating the development of new antimicrobials with reduced nephrotoxicity and improved efficacy.

Innovation Solution

Development of novel cyclic peptide compounds, including those of formula (I) and its derivatives, which are effective against polymyxin-resistant bacteria and fungi, offering reduced nephrotoxicity and improved stability, and can be used in pharmaceutical compositions for treating bacterial and fungal infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polymyxins are used to treat polymyxin-resistant bacteria, then treatment effectiveness is improved, but nephrotoxicity increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidnephrotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of polymyxin by changing specific parameters such as the side chain length (R1-R10 groups), ring structure variations (Y1-Y8), and substitution patterns (R1-R10) to create analogs with altered pharmacological properties that reduce nephrotoxicity while preserving antibacterial activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures combining the cyclic peptide core of polymyxin with various modified side chains and substituents (different R groups including alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups) to achieve optimized therapeutic profiles

Inventive Principle:

Principle #40Composite materials

2Reliability

If existing antibiotics are used to treat fungal infections, then treatment effectiveness is limited, but resistance development increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidresistance development

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops antimicrobial compounds with broad-spectrum activity that can effectively treat both bacterial and fungal infections, making the treatment versatile against multiple pathogen types including polymyxin-resistant bacteria and fungi, thereby reducing the need for pathogen-specific antibiotics and slowing resistance development

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Shape

If octapeptins are used as antibiotics, then structure similarity to polymyxins is achieved, but exploration as antibiotics against polymyxin-resistant bacteria is limited

Engineering Contradiction:

Improvestructural similarityVSAvoidantibacterial activity

Core Design Contradiction:

ShapeVSReliability

Solution Approach 1:

The patent applies local modifications to the octapeptin structure by varying specific positions (R1-R10 substituents, Y1-Y8 configurations, side chain lengths) while maintaining the overall cyclic peptide framework, creating localized structural variations that enhance antibacterial activity against polymyxin-resistant strains

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11279733B2Peptide antibiotics

Publication Date: 2022.03.22 THE UNIVERSITY OF QUEENSLAND

AI summary

There is provided a range of novel compounds. These novel compounds may demonstrate abroad spectrum antibacterial and antifungal activity. These compounds may be active against the emerging polymyxin resistant bacteria. These compounds may also be useful when used in conjunction with other pharmaceutically active agents.