New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00477657" target="_blank" >RIV/61388963:_____/17:00477657 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bmc.2017.06.046" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2017.06.046</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2017.06.046" target="_blank" >10.1016/j.bmc.2017.06.046</a>

Jazyk výsledku

angličtina

Název v původním jazyce

New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity

Popis výsledku v původním jazyce

New 2,4-diamino-6-[2-(phosphonomethoxy) ethoxy] pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy) ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME5- azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC50's of 0.15-1.12 mM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis (hexadecylamido-L-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug.

Název v anglickém jazyce

New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity

Popis výsledku anglicky

New 2,4-diamino-6-[2-(phosphonomethoxy) ethoxy] pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy) ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME5- azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC50's of 0.15-1.12 mM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis (hexadecylamido-L-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA14-00522S" target="_blank" >GA14-00522S: Syntézy nových prolékových forem biologicky aktivních nukleotidových analogů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Bioorganic & Medicinal Chemistry

ISSN

0968-0896

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

4637-4648

Kód UT WoS článku

000407831300010

EID výsledku v databázi Scopus

2-s2.0-85026313573