(Iso)Quinoline–Artemisinin Hybrids Prepared through Click Chemistry: Highly Potent Agents against Viruses

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00532154" target="_blank" >RIV/61388963:_____/20:00532154 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/chem.202001803" target="_blank" >https://doi.org/10.1002/chem.202001803</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/chem.202001803" target="_blank" >10.1002/chem.202001803</a>

Jazyk výsledku

angličtina

Název v původním jazyce

(Iso)Quinoline–Artemisinin Hybrids Prepared through Click Chemistry: Highly Potent Agents against Viruses

Popis výsledku v původním jazyce

Viral infections cause life‐threatening diseases in millions of people worldwide every year and there is an urgent need for new, effective antiviral drugs. Hybridization of two chemically diverse compounds into a new bioactive effector product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds. In this study, (iso)quinoline–artemisinin hybrids, obtained through copper‐catalyzed azide–alkyne cycloaddition or metal‐free click reactions (in organic solvents or in the presence of water), were analyzed in vitro, for the first time, for their inhibitory activity against human cytomegalovirus (HCMV), relative to their parent compounds and the reference drug ganciclovir. EC50 (HCMV) values were obtained in a range 0.22–1.20 μm, which indicated highly potent antiviral properties in the absence of cytotoxic effects on normal cells (CC50>100 μm). The most active hybrid, 1 (EC50=0.22 μm), is 25 times more potent than its parent compound artesunic acid (EC50=5.41 μm) and 12 times more efficient than the standard drug ganciclovir (EC50=2.6 μm). Interestingly, hybrid 1 also shows inhibitory activity against hepatitis B virus in vitro (EC50 (HBeAg)=2.57 μm).

Název v anglickém jazyce

(Iso)Quinoline–Artemisinin Hybrids Prepared through Click Chemistry: Highly Potent Agents against Viruses

Popis výsledku anglicky

Viral infections cause life‐threatening diseases in millions of people worldwide every year and there is an urgent need for new, effective antiviral drugs. Hybridization of two chemically diverse compounds into a new bioactive effector product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds. In this study, (iso)quinoline–artemisinin hybrids, obtained through copper‐catalyzed azide–alkyne cycloaddition or metal‐free click reactions (in organic solvents or in the presence of water), were analyzed in vitro, for the first time, for their inhibitory activity against human cytomegalovirus (HCMV), relative to their parent compounds and the reference drug ganciclovir. EC50 (HCMV) values were obtained in a range 0.22–1.20 μm, which indicated highly potent antiviral properties in the absence of cytotoxic effects on normal cells (CC50>100 μm). The most active hybrid, 1 (EC50=0.22 μm), is 25 times more potent than its parent compound artesunic acid (EC50=5.41 μm) and 12 times more efficient than the standard drug ganciclovir (EC50=2.6 μm). Interestingly, hybrid 1 also shows inhibitory activity against hepatitis B virus in vitro (EC50 (HBeAg)=2.57 μm).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemistry - A European Journal

ISSN

0947-6539

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

52

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

8

Strana od-do

12019-12026

Kód UT WoS článku

000563972100001

EID výsledku v databázi Scopus

2-s2.0-85089467356