New potent N‐hydroxycinnamamide‐based histone deacetylase
inhibitors suppress proliferation and trigger apoptosis in
THP‐1 leukaemia cells

J 2025

New potent N‐hydroxycinnamamide‐based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP‐1 leukaemia cells

ONUŠČÁKOVÁ, Magdaléna; Tereza KAUEROVÁ; Eva FIALOVÁ; Hana PÍŽOVÁ; Vladimír GARAJ et. al.

Základní údaje

Originální název

New potent N‐hydroxycinnamamide‐based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP‐1 leukaemia cells

Autoři

ONUŠČÁKOVÁ, Magdaléna; Tereza KAUEROVÁ; Eva FIALOVÁ; Hana PÍŽOVÁ; Vladimír GARAJ; Miroslav KEMKA; Vladimir FRECER; Peter KOLLÁR a Pavel BOBÁĽ

Vydání

Archiv der Pharmazie, Weinheim, 2025, 0365-6233

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.600 v roce 2024

Organizační jednotka

Farmaceutická fakulta

DOI

https://doi.org/10.1002/ardp.202400889

UT WoS

001456667500001

EID Scopus

2-s2.0-105002082514

Klíčová slova anglicky

anticancer agents; HDACi; haematological malignancies; hydroxamic acid; inhibitors of histone deacetylases

Štítky

rivok, ÚChL, ÚFTo

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 5. 2025 11:29, Mgr. Irena Doubková

Anotace

V originále

A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.

Návaznosti

MUNI/A/1598/2020, interní kód MU

Název: Analýza antiproliferačních, proapoptotických a cytodiferenciačních účinků nově syntetizovaných hydroxamových kyselin

Investor: Masarykova univerzita, Analýza antiproliferačních, proapoptotických a cytodiferenciačních účinků nově syntetizovaných hydroxamových kyselin

Citovat

ONUŠČÁKOVÁ, Magdaléna; Tereza KAUEROVÁ; Eva FIALOVÁ; Hana PÍŽOVÁ; Vladimír GARAJ; Miroslav KEMKA; Vladimir FRECER; Peter KOLLÁR a Pavel BOBÁĽ. New potent N‐hydroxycinnamamide‐based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP‐1 leukaemia cells. Archiv der Pharmazie. Weinheim, 2025, roč. 358, č. 4, s. 1-22. ISSN 0365-6233. Dostupné z: https://doi.org/10.1002/ardp.202400889.

@article{2496719,
   author = {Onuščáková, Magdaléna and Kauerová, Tereza and Fialová, Eva and Pížová, Hana and Garaj, Vladimír and Kemka, Miroslav and Frecer, Vladimir and Kollár, Peter and Bobáľ, Pavel},
   article_location = {Weinheim},
   article_number = {4},
   doi = {https://doi.org/10.1002/ardp.202400889},
   keywords = {anticancer agents; HDACi; haematological malignancies; hydroxamic acid; inhibitors of histone deacetylases},
   language = {eng},
   issn = {0365-6233},
   journal = {Archiv der Pharmazie},
   title = {New potent N‐hydroxycinnamamide‐based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP‐1 leukaemia cells},
   url = {https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400889},
   volume = {358},
   year = {2025}
}

TY  - JOUR
ID  - 2496719
AU  - Onuščáková, Magdaléna - Kauerová, Tereza - Fialová, Eva - Pížová, Hana - Garaj, Vladimír - Kemka, Miroslav - Frecer, Vladimir - Kollár, Peter - Bobáľ, Pavel
PY  - 2025
TI  - New potent N‐hydroxycinnamamide‐based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP‐1 leukaemia cells
JF  - Archiv der Pharmazie
VL  - 358
IS  - 4
SP  - 1-22
EP  - 1-22
SN  - 03656233
KW  - anticancer agents
KW  - HDACi
KW  - haematological malignancies
KW  - hydroxamic acid
KW  - inhibitors of histone deacetylases
UR  - https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400889
N2  - A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.
ER  -

ONUŠČÁKOVÁ, Magdaléna; Tereza KAUEROVÁ; Eva FIALOVÁ; Hana PÍŽOVÁ; Vladimír GARAJ; Miroslav KEMKA; Vladimir FRECER; Peter KOLLÁR a Pavel BOBÁĽ. New potent N‐hydroxycinnamamide‐based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP‐1 leukaemia cells. \textit{Archiv der Pharmazie}. Weinheim, 2025, roč.~358, č.~4, s.~1-22. ISSN~0365-6233. Dostupné z: https://doi.org/10.1002/ardp.202400889.

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