Persephacin Cyclic Depsipeptides for Drug-Resistant Fungal Infections
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Solution Overview
Problem
Current antifungal treatments are limited, with only a few classes of antifungal agents available, leading to challenges in addressing the rise of drug-resistant fungal pathogens, such as Candida auris and Aspergillus fumigatus, which poses a significant threat to human health.
Innovation Solution
Development of novel cyclic depsipeptide-class molecules, referred to as persephacins, which exhibit broad-spectrum antifungal activity by targeting diverse clinically relevant fungal pathogens, including Candida and Aspergillus species, through mechanisms different from existing treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antifungal agents (azoles, polyenes, pyrimidine analogs, echinocandins) are used to treat fungal infections, then treatment options are limited to four classes of drugs, but drug resistance among fungal pathogens rises rapidly
Solution Approach 1:
The patent introduces a novel class of antifungal agents (cyclic depsipeptides/persephacins) with a new mechanism of action that differs from existing drug classes. This changes the fundamental parameter of mechanism of action, providing an alternative pathway for fungal cell death that bypasses resistance mechanisms developed against traditional antifungals
Solution Approach 2:
The invention combines amino acids and hydroxy acids in specific cyclic depsipeptide structures to create molecules with novel antifungal properties. This composite molecular structure enables new interactions with fungal targets, expanding the versatility of antifungal treatment options
2Reliability
If novel antifungal agents with new mechanisms of action are developed, then drug resistance can be addressed, but the complexity of drug discovery and development increases
Solution Approach 1:
The cyclic depsipeptide structure is composed of repeating units of amino acids and hydroxy acids that can be systematically varied. This segmented modular structure allows for methodical exploration of structure-activity relationships, making the complexity manageable through systematic modification of discrete components
Solution Approach 2:
The patent systematically varies parameters such as the number and type of amino acid residues, the number and type of hydroxy acid residues, and the ring size to optimize antifungal activity. This structured parameter variation approach makes the development process more manageable despite the inherent complexity
Data Source
AI summary
Cyclic depsipeptide-class molecules, referred to herein as persephacins (including analogs thereof), having similarities to aureobasidin A, are described. The persephacins have antimicrobial activity, such as antifungal activity against a diverse range of clinically-relevant fungal pathogens, antiprotozoan parasite activity, and antibacterial activity, and can be used for example in treatments of difficult-to-treat ocular fungal infections at lower concentrations than natamycin. The active compounds may be combined with a secondary compound in a composition.