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Insight on the Pro-oxidant Capability of Amphotericin B in Lipid Media: A Theoretical Study
  • Manuel E. Medina,
  • Thuluz Meza-Menchaca,
  • Angel Trigos
Manuel E. Medina
Universidad Veracruzana
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Thuluz Meza-Menchaca
Universidad Veracruzana
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Angel Trigos
Universidad Veracruzana
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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.