Amphotericin B Tamed by Salicylic Acid

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Mycology

Background:

• Amphotericin B (AmB) is a critical antifungal agent for deep fungal infections.
• Severe hemolytic and nephrotoxic side effects limit Amphotericin B's clinical application.
• Developing safer AmB formulations is crucial for effective antifungal therapy.

Purpose of the Study:

• To synthesize and characterize novel Amphotericin B derivatives.
• To evaluate the antifungal efficacy and cytotoxicity of these new derivatives.
• To determine if salicylic acid modification can mitigate Amphotericin B's toxicity.

Main Methods:

• Synthesis of Amphotericin B-salicylic acid (AmB-SA) conjugates.
• Structural confirmation using NMR (¹H, ¹³C), HR-MS, and IR spectroscopy.
• In vitro antifungal activity testing against Candida albicans, Candida glabrata, and Cryptococcus neoformans.
• In vitro cytotoxicity assessment using HEK 293T cells and hemolytic toxicity assays.

Main Results:

• AmB-SA conjugates demonstrated potent antifungal activity comparable to Amphotericin B.
• Renal cytotoxicity in HEK 293T cells was significantly reduced for AmB-SA conjugates.
• Hemolytic toxicity was substantially decreased in the AmB-SA derivatives.
• Therapeutic window for AmB-SA conjugates showed minimal nephrotoxicity.

Conclusions:

• Modification of Amphotericin B with salicylic acid is an effective strategy to reduce toxicity.
• AmB-SA derivatives maintain broad-spectrum antifungal activity while enhancing safety.
• These novel AmB derivatives hold promise for future clinical application in treating fungal infections.