Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (2)

Search Parameters:
Keywords = aromatic polyene antifungals

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
25 pages, 9296 KB  
Article
Generation of New Glycoanalogues of Polyene Antibiotics by Synthetic Biology—Testing Current Technical Boundaries
by Mark Hogan, Yuhao Song, Jimmy Muldoon and Patrick Caffrey
SynBio 2024, 2(1), 31-55; https://doi.org/10.3390/synbio2010003 - 4 Jan 2024
Cited by 4 | Viewed by 4889
Abstract
A number of antifungal drugs are based on polyene macrolides that cause severe side effects. Most of these compounds contain a single aminodeoxysugar, D-mycosamine. Toxicity can be reduced by increasing the extent of glycosylation. The aromatic heptaene 67-121C and two analogues of the [...] Read more.
A number of antifungal drugs are based on polyene macrolides that cause severe side effects. Most of these compounds contain a single aminodeoxysugar, D-mycosamine. Toxicity can be reduced by increasing the extent of glycosylation. The aromatic heptaene 67-121C and two analogues of the degenerate heptaene nystatin have a second sugar attached to the C4′ hydroxyl of mycosamine. Another nystatin analogue has L-digitoxose as a second sugar attached to C35 on the macrolactone ring. The pentaene selvamicin has 4-O-methyl-L-digitoxose at C27, the equivalent position. To assist the production of new antifungals by synthetic biology, we explore further the utility of three classes of polyene glycosyltransferase: extending glycosyltransferases that form disaccharide-containing polyenes, glycosyltransferases that add the L-digitoxose sugars of nystatin A3 and selvamicin, and mycosaminyltransferases that add the primary aminodeoxysugar. In addition, we combine enzymatic hyperglycosylation with a known chemical method for adding sugars to the C3′ amino group of mycosamine. This was used to convert the disaccharide-containing 67-121C heptaene to forms containing branched trisaccharide or tetrasaccharide chains. These analogues are of interest for testing as anti-Leishmania drugs. Full article
Show Figures

Figure 1

15 pages, 5485 KB  
Article
Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics
by Julia Borzyszkowska-Bukowska, Justyna Górska, Paweł Szczeblewski, Tomasz Laskowski, Iwona Gabriel, Jakub Jurasz, Katarzyna Kozłowska-Tylingo, Piotr Szweda and Sławomir Milewski
Int. J. Mol. Sci. 2021, 22(18), 10108; https://doi.org/10.3390/ijms221810108 - 18 Sep 2021
Cited by 9 | Viewed by 3570
Abstract
Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans→ all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes [...] Read more.
Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans→ 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. Full article
(This article belongs to the Special Issue Advances in Molecular Activity of Potential Drugs)
Show Figures

Figure 1

Back to TopTop