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Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics
Abstract
Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans to all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes model. This effect was mainly due to the diminished hemotoxicity. The molecular modeling studies on interactions between original antibiotics and their photoisomers with ergosterol and cholesterol revealed some difference in free energy profiles of formation of binary antibiotic/sterol complexes in respective membrane environments. Moreover, different geometries of heptaene: sterol complexes and variations in polyene macrolide molecule alignment in cholesterol- and ergosterol-containing membranes were found. None of these effects are of the crucial importance for the observed improvement of selective toxicity of aromatic heptaene antifungals but each seems to provide a partial contribution.
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- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms221810108
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- Category:
- Articles
- Type:
- artykuły w czasopismach
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 22,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2021
- Bibliographic description:
- Borzyszkowska-Bukowska J., Górska J., Szczeblewski P., Laskowski T., Gabriel I., Jurasz J., Kozłowska-Tylingo K., Szweda P., Milewski S.: Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 22,iss. 18 (2021), s.10108-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms221810108
- Sources of funding:
- Verified by:
- Gdańsk University of Technology
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