| Autor: |
Vahid Barati, Anna Hruzíková, Eliška Procházková, Martin Zavřel, Jaroslav Kozák, Jana Trylčová, Dominik Rejman, Jan Weber, Kateřina Bogdanová, Milan Kolář, Ondřej Baszczyňski |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
European Journal of Medicinal Chemistry Reports, Vol 12, Iss , Pp 100216- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2772-4174 |
| DOI: |
10.1016/j.ejmcr.2024.100216 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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