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.

Basic information

Original name

Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance

Authors

FARSA, Oldřich (203 Czech Republic, belonging to the institution), Veronika BALLAYOVÁ (703 Slovakia, guarantor, belonging to the institution), Radka ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), Peter KOLLÁR (203 Czech Republic, belonging to the institution), Tereza KAUEROVÁ (203 Czech Republic, belonging to the institution) and Peter ZUBÁČ (703 Slovakia, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600

RIV identification code

RIV/00216224:14160/22:00126601

Organization unit

Faculty of Pharmacy

DOI

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

UT WoS

000851097400001

Keywords in English

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

Abstract

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.

Links

MUNI/A/1682/2020, interní kód MU

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

Investor: Masaryk University

MUNI/IGA/0932/2021, interní kód MU

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

Investor: Masaryk University

Citovat

FARSA, Oldřich, Veronika BALLAYOVÁ, Radka ŽÁČKOVÁ, Peter KOLLÁR, Tereza KAUEROVÁ and Peter ZUBÁČ. Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol. 23, No 17, p. 1-15. ISSN 1422-0067. Available from: 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 and Peter ZUBÁČ. Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol.~23, No~17, p.~1-15. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms23179813.

Detailed Information on Publication Record