Water-Soluble Nystatin and Derivative

Area of Science:

• Mycology
• Medicinal Chemistry
• Pharmacology

Background:

• Fungal infections cause significant morbidity and mortality, particularly in immunocompromised individuals.
• Emerging drug-resistant fungal strains present a growing clinical challenge.
• Nystatin, a polyene antifungal, has limitations in solubility and high toxicity, restricting its use.

Purpose of the Study:

• To develop novel Nystatin derivatives and formulations to overcome existing limitations.
• To enhance the therapeutic potential of Nystatin for broader clinical applications.

Main Methods:

• Synthesis of Nystatin amide derivatives and a deoxycholate formulation.
• Antifungal potency testing using USP(81) method and minimum inhibitory concentration (MIC) against Candida albicans and Aspergillus niger.
• In vitro toxicity and stability assessments of the novel compounds.

Main Results:

• An ethanol amide derivative of Nystatin was synthesized and found to be fully water-soluble (up to 100 mg/mL).
• This derivative demonstrated equivalent antifungal potency to Nystatin.
• The ethanol amide derivative exhibited 13.5 times lower in vitro toxicity compared to Nystatin.

Conclusions:

• The novel ethanol amide derivative of Nystatin represents a significant advancement.
• Its improved solubility, retained potency, and reduced toxicity make it a promising candidate for future antifungal drug development.
• This derivative could offer a safer and more effective treatment option for challenging fungal infections.