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Development of TrxR1 inhibitors yielded six new Ugi-Michael acceptors with anticancer effects in neuroblastoma cells

Jovanović, Mirna; Podolski-Renić, Ana; Zhukovsky, Danill; Nešović, Marija; Dragoj, Miodrag; Stanković, Tijana; Dinić, Jelena; Zalubovskis, Raivis; Krasavin, Mikhail; Pešić, Milica

(International society of Antioxidants, 2019)

TY  - CONF
AU  - Jovanović, Mirna
AU  - Podolski-Renić, Ana
AU  - Zhukovsky, Danill
AU  - Nešović, Marija
AU  - Dragoj, Miodrag
AU  - Stanković, Tijana
AU  - Dinić, Jelena
AU  - Zalubovskis, Raivis
AU  - Krasavin, Mikhail
AU  - Pešić, Milica
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6047
AB  - Introduction: Cancer cells have high expression of thioredoxin (Trx) system proteins - Tx and thioredoxin
reductase (TrxR) [1,2]. lnhibition of Trx system is a perspective target of chemotherapy development [3,4].
Here we describe biological effects of six new Ugi-Michael acceptors (UMAs), potential TrxR1 inhibitors, in
human neuroblastoma cell line (SH-SY5Y) and normal human keratinocytes (HaCaT).
Materials & Methods: lnhibitory potential of UMAs was assessed by TxR1 and insulin assay. Cytotoxicity
was determined by MTT assay. Flow cytometry was used to assess reactive oxygen and nitrogen species
(RONS) levels by DHE and DHR staining and to analyze cell death by AV/PI labeling.
Reults: TrxR1 and insulin assay proved that six novel UMAs are inhibitors of TrxR1 and Trx system. The
inhibitors of TrxR1 showed cytotoxic effect in both cell lines. However, UMAs evoked increase in RONS only in neuroblastoma cells, but not in keratinocytes. These compounds also induced necrotic cell death in both cell lines. lmportantly, cell death induction was more pronounced in SH-SY5Y cells and in accordance with observed elevation of RONS levels.
PB  - International society of Antioxidants
C3  - 21st lnternational Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants; 2019, Jun 20-21; Paris, France
T1  - Development of TrxR1 inhibitors yielded six new Ugi-Michael acceptors with anticancer effects in neuroblastoma cells
SP  - 102
EP  - 102
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6047
ER  - 
@conference{
author = "Jovanović, Mirna and Podolski-Renić, Ana and Zhukovsky, Danill and Nešović, Marija and Dragoj, Miodrag and Stanković, Tijana and Dinić, Jelena and Zalubovskis, Raivis and Krasavin, Mikhail and Pešić, Milica",
year = "2019",
abstract = "Introduction: Cancer cells have high expression of thioredoxin (Trx) system proteins - Tx and thioredoxin
reductase (TrxR) [1,2]. lnhibition of Trx system is a perspective target of chemotherapy development [3,4].
Here we describe biological effects of six new Ugi-Michael acceptors (UMAs), potential TrxR1 inhibitors, in
human neuroblastoma cell line (SH-SY5Y) and normal human keratinocytes (HaCaT).
Materials & Methods: lnhibitory potential of UMAs was assessed by TxR1 and insulin assay. Cytotoxicity
was determined by MTT assay. Flow cytometry was used to assess reactive oxygen and nitrogen species
(RONS) levels by DHE and DHR staining and to analyze cell death by AV/PI labeling.
Reults: TrxR1 and insulin assay proved that six novel UMAs are inhibitors of TrxR1 and Trx system. The
inhibitors of TrxR1 showed cytotoxic effect in both cell lines. However, UMAs evoked increase in RONS only in neuroblastoma cells, but not in keratinocytes. These compounds also induced necrotic cell death in both cell lines. lmportantly, cell death induction was more pronounced in SH-SY5Y cells and in accordance with observed elevation of RONS levels.",
publisher = "International society of Antioxidants",
journal = "21st lnternational Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants; 2019, Jun 20-21; Paris, France",
title = "Development of TrxR1 inhibitors yielded six new Ugi-Michael acceptors with anticancer effects in neuroblastoma cells",
pages = "102-102",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6047"
}
Jovanović, M., Podolski-Renić, A., Zhukovsky, D., Nešović, M., Dragoj, M., Stanković, T., Dinić, J., Zalubovskis, R., Krasavin, M.,& Pešić, M.. (2019). Development of TrxR1 inhibitors yielded six new Ugi-Michael acceptors with anticancer effects in neuroblastoma cells. in 21st lnternational Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants; 2019, Jun 20-21; Paris, France
International society of Antioxidants., 102-102.
https://hdl.handle.net/21.15107/rcub_ibiss_6047
Jovanović M, Podolski-Renić A, Zhukovsky D, Nešović M, Dragoj M, Stanković T, Dinić J, Zalubovskis R, Krasavin M, Pešić M. Development of TrxR1 inhibitors yielded six new Ugi-Michael acceptors with anticancer effects in neuroblastoma cells. in 21st lnternational Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants; 2019, Jun 20-21; Paris, France. 2019;:102-102.
https://hdl.handle.net/21.15107/rcub_ibiss_6047 .
Jovanović, Mirna, Podolski-Renić, Ana, Zhukovsky, Danill, Nešović, Marija, Dragoj, Miodrag, Stanković, Tijana, Dinić, Jelena, Zalubovskis, Raivis, Krasavin, Mikhail, Pešić, Milica, "Development of TrxR1 inhibitors yielded six new Ugi-Michael acceptors with anticancer effects in neuroblastoma cells" in 21st lnternational Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants; 2019, Jun 20-21; Paris, France (2019):102-102,
https://hdl.handle.net/21.15107/rcub_ibiss_6047 .