Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73616089" target="_blank" >RIV/61989592:15310/22:73616089 - isvavai.cz</a>
Výsledek na webu
<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202200180" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202200180</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.202200180" target="_blank" >10.1002/cmdc.202200180</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives
Popis výsledku v původním jazyce
The synthesis and biological evaluation of novel guanidino sugars as isonucleoside analogs is described. 5-Guanidino xylofuranoses containing 3-O-saturated/unsaturated hydrocarbon or aromatic-containing moieties were accessed from 5-azido xylofuranoses via reduction followed by guanidinylation with N,N '-bis(tert-butoxycarbonyl)-N ''-triflylguanidine. Molecules comprising novel types of isonucleosidic structures including 5-guanidino 3-O-methyl-branched N-benzyltriazole isonucleosides and a guanidinomethyltriazole 3 '-O-dodecyl xylofuranos-5 '-yl isonucleoside were accessed. The guanidinomethyltriazole derivative and a 3-O-dodecyl (N-Boc)guanidino xylofuranose were revealed as selective inhibitors of acetylcholinesterase (K-i=22.87 and 7.49 mu M, respectively). The latter also showed moderate antiproliferative effects in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells. An aminomethyltriazole 5'-isonucleoside was the most potent molecule with low micromolar GI(50) values in both cells (GI(50)=6.33 mu M, 8.45 mu M), similar to that of the drug 5-fluorouracil in MCF-7 cells. Moreover, the most bioactive compounds showed low toxicity in human fibroblasts, further indicating their interest as promising lead molecules.
Název v anglickém jazyce
Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives
Popis výsledku anglicky
The synthesis and biological evaluation of novel guanidino sugars as isonucleoside analogs is described. 5-Guanidino xylofuranoses containing 3-O-saturated/unsaturated hydrocarbon or aromatic-containing moieties were accessed from 5-azido xylofuranoses via reduction followed by guanidinylation with N,N '-bis(tert-butoxycarbonyl)-N ''-triflylguanidine. Molecules comprising novel types of isonucleosidic structures including 5-guanidino 3-O-methyl-branched N-benzyltriazole isonucleosides and a guanidinomethyltriazole 3 '-O-dodecyl xylofuranos-5 '-yl isonucleoside were accessed. The guanidinomethyltriazole derivative and a 3-O-dodecyl (N-Boc)guanidino xylofuranose were revealed as selective inhibitors of acetylcholinesterase (K-i=22.87 and 7.49 mu M, respectively). The latter also showed moderate antiproliferative effects in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells. An aminomethyltriazole 5'-isonucleoside was the most potent molecule with low micromolar GI(50) values in both cells (GI(50)=6.33 mu M, 8.45 mu M), similar to that of the drug 5-fluorouracil in MCF-7 cells. Moreover, the most bioactive compounds showed low toxicity in human fibroblasts, further indicating their interest as promising lead molecules.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30107 - Medicinal chemistry
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
ChemMedChem
ISSN
1860-7179
e-ISSN
1860-7187
Svazek periodika
17
Číslo periodika v rámci svazku
14
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
11
Strana od-do
"e202200180-1"-"e202200180-11"
Kód UT WoS článku
000804905400001
EID výsledku v databázi Scopus
2-s2.0-85131153304