Insight on the Pro-oxidant Capability of Amphotericin B in Lipid Media:
A Theoretical Study
Abstract
A study of the pro-oxidant capacity of amphotericin B was carried out by
analyzing the photosensitizing ability of an amphotericin B model.
Although amphotericin B is a well-known broad-spectrum antibiotic,
little is known about the mechanism of its pro-oxidant capability. This
study employed density functional theory to assess the photosensitizing
capacity of AMP. Furthermore, electron transfer reactions were modeled
according to the Marcus theory, considering that lipid media can mimic
the environment of the cell membrane. The results show that AMP is a
pro-oxidant molecule mainly through the type II mechanism, with the
corresponding production of 1O2. In this way, AMP could induce oxidative
stress because it is capable of generating reactive oxygen species. In
this case, AMP showed a reaction rate constants of 8.94 x 109 and 1.89 x
1010 M−1 s−1 for the type I and II mechanisms, respectively, while the
overall reaction rate constant was 2.79 x 1010 M−1 s−1. Therefore, the
results of this study support the pro-oxidant capacity of amphotericin B
in lipid media, and considering that ergosterol is more susceptible to
undergoing oxidative damage by reactive oxygen species than cholesterol,
this mechanism could contribute to the antifungal activity of
amphotericin B.