Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F23%3A43927428" target="_blank" >RIV/60461373:22310/23:43927428 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0968089623003565?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0968089623003565?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2023.117508" target="_blank" >10.1016/j.bmc.2023.117508</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir

Popis výsledku v původním jazyce

Adefovir based acyclic nucleoside phosphonates were previously shown to modulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC50 = 4.45 μM), non-toxic, and selective mAC2 inhibitor (vs. mAC1 and mAC5). Such a compound represents a valuable addition to a limited number of small-molecule probes to study the biological functions of individual endogenous mAC isoforms.

Název v anglickém jazyce

Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir

Popis výsledku anglicky

Adefovir based acyclic nucleoside phosphonates were previously shown to modulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC50 = 4.45 μM), non-toxic, and selective mAC2 inhibitor (vs. mAC1 and mAC5). Such a compound represents a valuable addition to a limited number of small-molecule probes to study the biological functions of individual endogenous mAC isoforms.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

BIOORGANIC &amp; MEDICINAL CHEMISTRY LETTERS

ISSN

0960-894X

e-ISSN

1464-3405

Svazek periodika

95

Číslo periodika v rámci svazku

15 November 2023

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

18

Strana od-do

117508

Kód UT WoS článku

001107116900001

EID výsledku v databázi Scopus

2-s2.0-85175552252