In vitro evaluation of antifungal and cytotoxic activities as also the therapeutic safety of the oxidized form of amphotericin B

• AmB-Ox is formed by catalytic effect of FeIII ions, methemoglobin and hemin.
• The biological properties of AmB-Ox were evaluated.
• AmB-Ox exhibited reduced antifungal and cytotoxic activities compared to AmB.
• AmB-Ox lost antifungal activity more effectively than cytotoxic activity.
• AmB-Ox possessed lower therapeutic safety in vitro than AmB.

The aim of this study was to evaluate the antifungal and cytotoxic activities of the oxidized form of amphotericin B (AmB-Ox) as well as to determine whether oxidation process of AmB is therapeutically beneficial in vitro. The antifungal activity was estimated against Candida albicans ATCC 10231 and Candida parasilosis ATCC 22019 by broth microdilution method according to the NCCLS M27-A2 standards. The in vitro cytotoxicity was evaluated using normal green monkey kidney cells (GMK) by MTT assay. The obtained results demonstrated that AmB-Ox possesses 16-fold decreased antifungal properties against the two Candida strains and 5-fold lower cytotoxic activity towards GMK cells in comparison with AmB.The therapeutic safety in vitro assessed by calculating the ratio between cytotoxicity (CC50 value) to antifungal activity (MIC value) showed that oxidation of AmB is a very unfavourable process in vitro, because leads to formation of derivative (AmB-Ox) that lost antifungal properties much more rapidly than cytotoxic activity. Thus, the process of the oxidation of AmB in vivo (if it occurs) can be also highly harmful for patient.

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