Aminopeptidase N Inhibitors as Pointers for Overcoming
Antitumor Treatment Resistance

J 2022

Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance

FARSA, Oldřich, Veronika BALLAYOVÁ, Radka ŽÁČKOVÁ, Peter KOLLÁR, Tereza KAUEROVÁ et. al.

Základní údaje

Originální název

Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance

Autoři

FARSA, Oldřich (203 Česká republika, domácí), Veronika BALLAYOVÁ (703 Slovensko, garant, domácí), Radka ŽÁČKOVÁ (203 Česká republika, domácí), Peter KOLLÁR (203 Česká republika, domácí), Tereza KAUEROVÁ (203 Česká republika, domácí) a Peter ZUBÁČ (703 Slovensko, domácí)

Vydání

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2022, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600

Kód RIV

RIV/00216224:14160/22:00126601

Organizační jednotka

Farmaceutická fakulta

DOI

http://dx.doi.org/10.3390/ijms23179813

UT WoS

000851097400001

Klíčová slova anglicky

aminopeptidase N; acetamidophenones; Schiff bases; semicarbazones; thiosemicarbazones; inhibition of proliferation

Štítky

rivok, ÚChL, ÚFTo

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 2. 2023 13:58, JUDr. Sabina Krejčiříková

Anotace

V originále

Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme.

Návaznosti

MUNI/A/1682/2020, interní kód MU

Název: Návrh, syntéza a hodnocení derivátů skupin léčiv s inhibiční enzymatickou aktivitou

Investor: Masarykova univerzita, Návrh, syntéza a hodnocení derivátů skupin léčiv s inhibiční enzymatickou aktivitou

MUNI/IGA/0932/2021, interní kód MU

Název: Basic ketones and their derivatives as potential anti-infective and anti-tumor drugs

Investor: Masarykova univerzita, Basic ketones and their derivatives as potential anti-infective and anti-tumor drugs

Citovat

FARSA, Oldřich, Veronika BALLAYOVÁ, Radka ŽÁČKOVÁ, Peter KOLLÁR, Tereza KAUEROVÁ a Peter ZUBÁČ. Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2022, roč. 23, č. 17, s. 1-15. ISSN 1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms23179813.

@article{2216037,
   author = {Farsa, Oldřich and Ballayová, Veronika and Žáčková, Radka and Kollár, Peter and Kauerová, Tereza and Zubáč, Peter},
   article_location = {Basel},
   article_number = {17},
   doi = {http://dx.doi.org/10.3390/ijms23179813},
   keywords = {aminopeptidase N; acetamidophenones; Schiff bases; semicarbazones; thiosemicarbazones; inhibition of proliferation},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance},
   url = {https://www.mdpi.com/1422-0067/23/17/9813/htm},
   volume = {23},
   year = {2022}
}

TY  - JOUR
ID  - 2216037
AU  - Farsa, Oldřich - Ballayová, Veronika - Žáčková, Radka - Kollár, Peter - Kauerová, Tereza - Zubáč, Peter
PY  - 2022
TI  - Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance
JF  - International Journal of Molecular Sciences
VL  - 23
IS  - 17
SP  - 1-15
EP  - 1-15
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - aminopeptidase N
KW  - acetamidophenones
KW  - Schiff bases
KW  - semicarbazones
KW  - thiosemicarbazones
KW  - inhibition of proliferation
UR  - https://www.mdpi.com/1422-0067/23/17/9813/htm
N2  - Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme.
ER  -

FARSA, Oldřich, Veronika BALLAYOVÁ, Radka ŽÁČKOVÁ, Peter KOLLÁR, Tereza KAUEROVÁ a Peter ZUBÁČ. Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2022, roč.~23, č.~17, s.~1-15. ISSN~1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms23179813.

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