Prodrugging fungicidal amphotericin B significantly decreases its toxic effects
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00603177" target="_blank" >RIV/61388963:_____/25:00603177 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/25:00603177 RIV/00216208:11310/25:10496411
Result on the web
<a href="https://doi.org/10.1016/j.ejmech.2024.117157" target="_blank" >https://doi.org/10.1016/j.ejmech.2024.117157</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2024.117157" target="_blank" >10.1016/j.ejmech.2024.117157</a>
Alternative languages
Result language
angličtina
Original language name
Prodrugging fungicidal amphotericin B significantly decreases its toxic effects
Original language description
Amphotericin B (AmB) is one of the most effective antifungal drugs, with a strong, dose-dependent activity against most Candida and Aspergillus species responsible for life-threatening infections. However, AmB is severely toxic, which hinders its broad use. In this proof-of-concept study, we demonstrate that prodrugging AmB considerably decreases AmB toxicity without affecting its fungicidal activity. For this purpose, we modified the AmB structure by attaching a designer phosphate promoiety, thereby switching off its mode of action and preventing its toxic effects. The original fungicidal activity of AmB was then restored upon prodrug activation by host plasma enzymes. These AmB prodrugs showed a safer toxicity profile than commercial AmB deoxycholate in Candida and Aspergillus species and significantly prolonged larval survival of infected Galleria mellonella larvae. Based on these findings, prodrugging toxic antifungals may be a viable strategy for broadening the antifungal arsenal, opening up opportunities for targeted prodrug design.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
1768-3254
Volume of the periodical
283
Issue of the periodical within the volume
February
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
13
Pages from-to
117157
UT code for WoS article
001411696400001
EID of the result in the Scopus database
2-s2.0-85211741691