HPMA-based polymer conjugates for repurposed drug mebendazole and other imidazole-based therapeutics
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F21%3A00545100" target="_blank" >RIV/61389013:_____/21:00545100 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.mdpi.com/2073-4360/13/15/2530" target="_blank" >https://www.mdpi.com/2073-4360/13/15/2530</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/polym13152530" target="_blank" >10.3390/polym13152530</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
HPMA-based polymer conjugates for repurposed drug mebendazole and other imidazole-based therapeutics
Popis výsledku v původním jazyce
Recently, the antitumor potential of benzimidazole anthelmintics, such as mebendazole and its analogues, have been reported to have minimal side effects, in addition to their well-known anti-parasitic abilities. However, their administration is strongly limited owing to their extremely poor solubility, which highly depletes their overall bioavailability. This study describes the design, synthesis, and physico-chemical properties of polymer-mebendazole nanomedicines for drug repurposing in cancer therapy. The conjugation of mebendazole to water-soluble and biocompatible polymer carrier was carried out via biodegradable bond, relying on the hydrolytic action of lysosomal hydrolases for mebendazole release inside the tumor cells. Five low-molecular-weight mebendazole derivatives, differing in their inner structure, and two polymer conjugates differing in their linker structure, were synthesized. The overall synthetic strategy was designed to enable the modification and polymer conjugation of most benzimidazole-based anthelmintics, such as albendazole, fenbendazole or albendazole, besides the mebendazole. Furthermore, the described methodology may be suitable for conjugation of other biologically active compounds with a heterocyclic N-H group in their molecules.
Název v anglickém jazyce
HPMA-based polymer conjugates for repurposed drug mebendazole and other imidazole-based therapeutics
Popis výsledku anglicky
Recently, the antitumor potential of benzimidazole anthelmintics, such as mebendazole and its analogues, have been reported to have minimal side effects, in addition to their well-known anti-parasitic abilities. However, their administration is strongly limited owing to their extremely poor solubility, which highly depletes their overall bioavailability. This study describes the design, synthesis, and physico-chemical properties of polymer-mebendazole nanomedicines for drug repurposing in cancer therapy. The conjugation of mebendazole to water-soluble and biocompatible polymer carrier was carried out via biodegradable bond, relying on the hydrolytic action of lysosomal hydrolases for mebendazole release inside the tumor cells. Five low-molecular-weight mebendazole derivatives, differing in their inner structure, and two polymer conjugates differing in their linker structure, were synthesized. The overall synthetic strategy was designed to enable the modification and polymer conjugation of most benzimidazole-based anthelmintics, such as albendazole, fenbendazole or albendazole, besides the mebendazole. Furthermore, the described methodology may be suitable for conjugation of other biologically active compounds with a heterocyclic N-H group in their molecules.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10404 - Polymer science
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Polymers
ISSN
2073-4360
e-ISSN
2073-4360
Svazek periodika
13
Číslo periodika v rámci svazku
15
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
14
Strana od-do
2530
Kód UT WoS článku
000682200100001
EID výsledku v databázi Scopus
2-s2.0-85111635782