Interaction between nystatin and natural membrane lipids in Langmuir monolayers--the role of a phospholipid in the mechanism of polyenes mode of action.
Nystatin (NYS), a polyene antifungal antibiotic, has been investigated in Langmuir monolayers alone and in mixtures with mammalian and fungi membrane sterols (cholesterol and ergosterol, respectively) as well as with a model phospholipid (DPPC). The interactions between film molecules have been examined both in a qualitative and quantitative way with the excess area per molecule (AExc), excess free energy of mixing (DeltaGExc) and the interaction parameter (alpha). The obtained results have been compared with those previously reported for another polyene antimycotic: amphotericin B (AmB) mixed with lipids. Higher affinity of NYS has been observed for ergosterol vs. cholesterol, however, the strongest attractions were found for its mixtures with DPPC. The obtained results have been verified with biological studies reported previously for both antibiotics (NYS and AmB). A thorough analysis of the Langmuir experiment results performed for both polyenes enabled us to conclude that the presence of DPPC can be considered as a key factor affecting their antifungal activity as well as their toxicity towards host cells.
Hac-Wydro
Katarzyna
K
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland. hac@chemia.uj.edu.pl
Dynarowicz-Latka
Patrycja
P
D000666:Amphotericin B / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002784:Cholesterol / Q000737:chemistry; D004875:Ergosterol / Q000737:chemistry; D005658:Fungi / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D015394:Molecular Structure; D009761:Nystatin / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011090:Polyenes / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013499:Surface Properties
D008563:Membrane Lipids; D008567:Membranes, Artificial; D010743:Phospholipids; D011090:Polyenes; D009761:Nystatin; D000666:Amphotericin B; D002784:Cholesterol; D004875:Ergosterol