Delivery of N-heterocyclic drugs, acids, phenols, and thiols via Tailor−made Self−immolative linkers

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00598593" target="_blank" >RIV/61388963:_____/24:00598593 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/24:10487531
Result on the web
<a href="https://doi.org/10.1016/j.ejmcr.2024.100216" target="_blank" >https://doi.org/10.1016/j.ejmcr.2024.100216</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmcr.2024.100216" target="_blank" >10.1016/j.ejmcr.2024.100216</a>

Result language
angličtina
Original language name
Delivery of N-heterocyclic drugs, acids, phenols, and thiols via Tailor−made Self−immolative linkers
Original language description
Heterocyclic drugs display diverse pharmacological activities and metabolic stability. However, their poor solubility and pharmacokinetic properties often compromise bioavailability and clinical outcomes. Nevertheless, the prodrug approach provides a viable strategy to overcome unwanted attributes of drug candidates. In this proof-of-concept study, we report the synthesis and biological evaluation of glycol methylene-bridged phosphate (GMBP) prodrugs developed for heterocyclic drug delivery. Through methylene bridging, the heterocyclic nitrogen was directly attached to the phosphate, whereas the glycol moiety enabled drug release via cyclization, as confirmed by 31P NMR spectroscopy. Additional prodrugs of carboxylic acids, phenols, and thiols confirmed the broad application scope of our GMPB approach. Heterocyclic GMBP prodrugs were stable in aqueous buffers and activated by phospholipase CAL-B in vitro. Select prodrugs, including zidovudine prodrug 33, were even more potent (3 nM on HIV-1) than the parent compound. These findings demonstrate that our GMBP approach is not only feasible but also highly versatile.
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
10401 - Organic chemistry

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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