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.
Authors
- dr inż. Julia Borzyszkowska-Bukowska link open in new tab ,
- Justyna Górska link open in new tab ,
- dr inż. Paweł Szczeblewski link open in new tab ,
- dr hab. inż. Tomasz Laskowski link open in new tab ,
- dr hab. inż. Iwona Gabriel link open in new tab ,
- Jakub Jurasz link open in new tab ,
- dr inż. Katarzyna Kozłowska-Tylingo link open in new tab ,
- dr hab. inż. Piotr Szweda link open in new tab ,
- prof. dr hab. inż. Sławomir Milewski link open in new tab
Additional information
- DOI
- Digital Object Identifier link open in new tab 10.3390/ijms221810108
- Category
- Publikacja w czasopiśmie
- Type
- artykuły w czasopismach
- Language
- angielski
- Publication year
- 2021
