Galactomannan-amphotericin B conjugate: synthesis and biological activity

Polysaccharide conjugated amphotericin B (AmB) was synthesized by conjugation of AmB to oxidized galactomannan (GM) by reductive amination and tested for antifungal activity. AmB conjugates were investigated for their ability to inhibit Candida albicans growth. Antifungal efficiency of the synthetic AmB-GM depends on both, AmB content and duration of exposure. The most potent compound was a conjugate which contains 40% AmB with minimal inhibition concentration of 0.25 mg/l. In vitro toxicity analysis revealed that conjugates with 20, 30, and 40% w/w AmB content have no hemolytic effect and no influence on the viability of the VERO kidney cells. Furthermore, maximal tolerant dose (MTD) of the conjugate was determined in vivo and found to be 60 mg/kg (equivalent to AmB), while commercial Fungizone (R) demonstrated increased toxicity of 3 mg/kg on mice model. Copyright (C) 2010 John Wiley & Sons, Ltd.