Evaluating Antimalarial Proteasome Inhibitors for Efficacy in Babesia Blood Stage Cultures

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F24%3A00601793" target="_blank" >RIV/60077344:_____/24:00601793 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/24:00601793 RIV/60076658:12310/24:43908696
Result on the web
<a href="https://doi.org/10.1021/acsomega.4c04564" target="_blank" >https://doi.org/10.1021/acsomega.4c04564</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsomega.4c04564" target="_blank" >10.1021/acsomega.4c04564</a>

Result language
angličtina
Original language name
Evaluating Antimalarial Proteasome Inhibitors for Efficacy in Babesia Blood Stage Cultures
Original language description
Tick-transmitted Babesia are a major global veterinary threat and an emerging risk to humans. Unlike their Plasmodium relatives, these erythrocyte-infecting Apicomplexa have been largely overlooked and lack specific treatment. Selective targeting of the Babesia proteasome holds promise for drug development. In this study, we screened a library of peptide epoxyketone inhibitors derived from the marine natural product carmaphycin B for their activity against Babesia. Several of these compounds showed activity against both the asexual and sexual blood stages of Plasmodium falciparum. These compounds inactivate beta 5 proteasome subunit activity in the lysates of Babesia divergens and Babesia microti in the low nanomolar range. Several compounds were tested with the purified B. divergens proteasome and showed IC50 values comparable to carfilzomib, an approved anticancer proteasome inhibitor. They also inhibited B. divergens growth in bovine erythrocyte cultures with solid EC50 values, but importantly, they appeared less toxic to human cells than carfilzomib. These compounds therefore offer a wider therapeutic window and provide new insights into the development of small proteasome inhibitors as selective drugs for babesiosis.
Czech name
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Czech description
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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
10606 - Microbiology

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

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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