TY  - JOUR
AU  - Jovanović, Mirna
AU  - Podolski-Renić, Ana
AU  - Krasavin, Mikhail
AU  - Pešić, Milica
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4991
AB  - The intracellular redox homeostasis is a dynamic balancing system between the levels of free radical species and antioxidant enzymes and small molecules at the core of cellular defense mechanisms. The thioredoxin (Trx) system is an important detoxification system regulating the redox milieu. This system is one of the key regulators of cells’ proliferative potential as well, through the reduction of key proteins. Increased oxidative stress characterizes highly proliferative, metabolically hyperactive cancer cells, which are forced to mobilize antioxidant enzymes to balance the increase in free radical concentration and prevent irreversible damage and cell death. Components of the Trx system are involved in high-rate proliferation and activation of pro-survival mechanisms in cancer cells, particularly those facing increased oxidative stress. This review addresses the importance of the targetable redox-regulating Trx system in tumor progression, as well as in detoxification and protection of cancer cells from oxidative stress and drug-induced cytotoxicity. It also discusses the cancer cells’ counteracting mechanisms to the Trx system inhibition and presents several inhibitors of the Trx system as prospective candidates for cytostatics’ adjuvants. This manuscript further emphasizes the importance of developing novel multitarget therapies encompassing the Trx system inhibition to overcome cancer treatment limitations.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Molecular Biosciences
T1  - The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance
VL  - 9
DO  - 10.3389/fmolb.2022.883297
SP  - 883297
ER  - 

@article{
author = "Jovanović, Mirna and Podolski-Renić, Ana and Krasavin, Mikhail and Pešić, Milica",
year = "2022",
abstract = "The intracellular redox homeostasis is a dynamic balancing system between the levels of free radical species and antioxidant enzymes and small molecules at the core of cellular defense mechanisms. The thioredoxin (Trx) system is an important detoxification system regulating the redox milieu. This system is one of the key regulators of cells’ proliferative potential as well, through the reduction of key proteins. Increased oxidative stress characterizes highly proliferative, metabolically hyperactive cancer cells, which are forced to mobilize antioxidant enzymes to balance the increase in free radical concentration and prevent irreversible damage and cell death. Components of the Trx system are involved in high-rate proliferation and activation of pro-survival mechanisms in cancer cells, particularly those facing increased oxidative stress. This review addresses the importance of the targetable redox-regulating Trx system in tumor progression, as well as in detoxification and protection of cancer cells from oxidative stress and drug-induced cytotoxicity. It also discusses the cancer cells’ counteracting mechanisms to the Trx system inhibition and presents several inhibitors of the Trx system as prospective candidates for cytostatics’ adjuvants. This manuscript further emphasizes the importance of developing novel multitarget therapies encompassing the Trx system inhibition to overcome cancer treatment limitations.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Molecular Biosciences",
title = "The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance",
volume = "9",
doi = "10.3389/fmolb.2022.883297",
pages = "883297"
}

Jovanović, M., Podolski-Renić, A., Krasavin, M.,& Pešić, M.. (2022). The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance. in Frontiers in Molecular Biosciences
Lausanne: Frontiers Media SA., 9, 883297.
https://doi.org/10.3389/fmolb.2022.883297

Jovanović M, Podolski-Renić A, Krasavin M, Pešić M. The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance. in Frontiers in Molecular Biosciences. 2022;9:883297.
doi:10.3389/fmolb.2022.883297 .

Jovanović, Mirna, Podolski-Renić, Ana, Krasavin, Mikhail, Pešić, Milica, "The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance" in Frontiers in Molecular Biosciences, 9 (2022):883297,
https://doi.org/10.3389/fmolb.2022.883297 . .

TY  - JOUR
AU  - Jovanović, Mirna
AU  - Dragoj, Miodrag
AU  - Zhukovsky, Daniil
AU  - Dar’in, Dmitry
AU  - Krasavin, Mikhail
AU  - Pešić, Milica
AU  - Podolski-Renić, Ana
PY  - 2020
UR  - https://www.frontiersin.org/article/10.3389/fmolb.2020.586146/full
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3944
AB  - Currently available glioblastoma (GBM) treatment remains ineffective, with relapse after initial response and low survival rate of GBM patients. Reasons behind limited capacities for GBM treatment are high tumor heterogeneity, invasiveness and occurrence of drug resistance. Therefore, developing novel therapeutic strategies is of utmost importance. Thioredoxin reductase (TrxR) is a novel, promising target due to its overexpression in many cancer types and important role in cancer progression. Previous research on Ugi-type Michael acceptors– inhibitors of TrxR, showed desirable anticancer properties, with significant selectivity towards cancer cells. Herein, two TrxR inhibitors, 5 and 6 underwent in depth study on multidrug resistant (MDR) glioma cell lines. Besides antioxidative effect, 5 and 6 induced cell death, decreased cell proliferation, suppressed invasion and migration of glioma cells. Both compounds showed a synergistic effect in combination with temozolomide (TMZ), a first line chemotherapeutic for GBM treatment. Moreover, 5 and 6 affected the activity of P-glycoprotein extrusion pump that could be found on cancer cells and in blood-brain barrier (BBB), thus showing potential for suppressing MDR phenotype in cancer cells and evading BBB. In conclusion, investigated TrxR inhibitors are effective anticancer compounds, acting through inhibition of thioredoxin system and perturbation of antioxidative defense systems of glioma cells. They are suitable for combining with other chemotherapeutics, able to surpass the BBB and overcome MDR. Thus our findings suggest further exploration of Ugi-type Michael acceptors-TrxR inhibitors’ potential as adjuvant therapy for GBM treatment.
PB  - Frontiers Media SA
T2  - Frontiers in Molecular Biosciences
T1  - Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy
VL  - 7
DO  - 10.3389/fmolb.2020.586146
SP  - 281
ER  - 

@article{
author = "Jovanović, Mirna and Dragoj, Miodrag and Zhukovsky, Daniil and Dar’in, Dmitry and Krasavin, Mikhail and Pešić, Milica and Podolski-Renić, Ana",
year = "2020",
abstract = "Currently available glioblastoma (GBM) treatment remains ineffective, with relapse after initial response and low survival rate of GBM patients. Reasons behind limited capacities for GBM treatment are high tumor heterogeneity, invasiveness and occurrence of drug resistance. Therefore, developing novel therapeutic strategies is of utmost importance. Thioredoxin reductase (TrxR) is a novel, promising target due to its overexpression in many cancer types and important role in cancer progression. Previous research on Ugi-type Michael acceptors– inhibitors of TrxR, showed desirable anticancer properties, with significant selectivity towards cancer cells. Herein, two TrxR inhibitors, 5 and 6 underwent in depth study on multidrug resistant (MDR) glioma cell lines. Besides antioxidative effect, 5 and 6 induced cell death, decreased cell proliferation, suppressed invasion and migration of glioma cells. Both compounds showed a synergistic effect in combination with temozolomide (TMZ), a first line chemotherapeutic for GBM treatment. Moreover, 5 and 6 affected the activity of P-glycoprotein extrusion pump that could be found on cancer cells and in blood-brain barrier (BBB), thus showing potential for suppressing MDR phenotype in cancer cells and evading BBB. In conclusion, investigated TrxR inhibitors are effective anticancer compounds, acting through inhibition of thioredoxin system and perturbation of antioxidative defense systems of glioma cells. They are suitable for combining with other chemotherapeutics, able to surpass the BBB and overcome MDR. Thus our findings suggest further exploration of Ugi-type Michael acceptors-TrxR inhibitors’ potential as adjuvant therapy for GBM treatment.",
publisher = "Frontiers Media SA",
journal = "Frontiers in Molecular Biosciences",
title = "Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy",
volume = "7",
doi = "10.3389/fmolb.2020.586146",
pages = "281"
}

Jovanović, M., Dragoj, M., Zhukovsky, D., Dar’in, D., Krasavin, M., Pešić, M.,& Podolski-Renić, A.. (2020). Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy. in Frontiers in Molecular Biosciences
Frontiers Media SA., 7, 281.
https://doi.org/10.3389/fmolb.2020.586146

Jovanović M, Dragoj M, Zhukovsky D, Dar’in D, Krasavin M, Pešić M, Podolski-Renić A. Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy. in Frontiers in Molecular Biosciences. 2020;7:281.
doi:10.3389/fmolb.2020.586146 .

Jovanović, Mirna, Dragoj, Miodrag, Zhukovsky, Daniil, Dar’in, Dmitry, Krasavin, Mikhail, Pešić, Milica, Podolski-Renić, Ana, "Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy" in Frontiers in Molecular Biosciences, 7 (2020):281,
https://doi.org/10.3389/fmolb.2020.586146 . .

TY  - JOUR
AU  - Jovanović, Mirna
AU  - Zhukovsky, Daniil
AU  - Podolski-Renić, Ana
AU  - Žalubovskis, Raivis
AU  - Dar'in, Dmitry
AU  - Sharoyko, Vladimir
AU  - Tennikova, Tatiana
AU  - Pešić, Milica
AU  - Krasavin, Mikhail
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3614
AB  - A series of analogs of the earlier reported lead compound DVD-445 (thioredoxin reductase inhibitor with anticancer activity) has been synthesized via a modified Ugi reaction and investigated. Seven most potent compounds (with IC50 below 5.00 μM against recombinant rTrxR1 enzyme) were examined for their effect on cell growth and viability, oxidative stress induction and P-glycoprotein (P-gp) inhibition in human glioblastoma cells cell line U87 and its corresponding multidrug resistant (MDR) cell line U87-TxR. Several of these frontrunner compounds were shown to be superior over DVD-445. Besides providing promising candidates for anticancer therapy, our study further validates the small electrophilic Ugi Michael acceptor (UMA) chemotype as efficacious inhibitor of thioredoxin reductase.
T2  - European Journal of Medicinal Chemistry
T1  - Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential.
VL  - 191
DO  - 10.1016/j.ejmech.2020.112119
SP  - 112119
ER  - 

@article{
author = "Jovanović, Mirna and Zhukovsky, Daniil and Podolski-Renić, Ana and Žalubovskis, Raivis and Dar'in, Dmitry and Sharoyko, Vladimir and Tennikova, Tatiana and Pešić, Milica and Krasavin, Mikhail",
year = "2020",
abstract = "A series of analogs of the earlier reported lead compound DVD-445 (thioredoxin reductase inhibitor with anticancer activity) has been synthesized via a modified Ugi reaction and investigated. Seven most potent compounds (with IC50 below 5.00 μM against recombinant rTrxR1 enzyme) were examined for their effect on cell growth and viability, oxidative stress induction and P-glycoprotein (P-gp) inhibition in human glioblastoma cells cell line U87 and its corresponding multidrug resistant (MDR) cell line U87-TxR. Several of these frontrunner compounds were shown to be superior over DVD-445. Besides providing promising candidates for anticancer therapy, our study further validates the small electrophilic Ugi Michael acceptor (UMA) chemotype as efficacious inhibitor of thioredoxin reductase.",
journal = "European Journal of Medicinal Chemistry",
title = "Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential.",
volume = "191",
doi = "10.1016/j.ejmech.2020.112119",
pages = "112119"
}

Jovanović, M., Zhukovsky, D., Podolski-Renić, A., Žalubovskis, R., Dar'in, D., Sharoyko, V., Tennikova, T., Pešić, M.,& Krasavin, M.. (2020). Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential.. in European Journal of Medicinal Chemistry, 191, 112119.
https://doi.org/10.1016/j.ejmech.2020.112119

Jovanović M, Zhukovsky D, Podolski-Renić A, Žalubovskis R, Dar'in D, Sharoyko V, Tennikova T, Pešić M, Krasavin M. Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential.. in European Journal of Medicinal Chemistry. 2020;191:112119.
doi:10.1016/j.ejmech.2020.112119 .

Jovanović, Mirna, Zhukovsky, Daniil, Podolski-Renić, Ana, Žalubovskis, Raivis, Dar'in, Dmitry, Sharoyko, Vladimir, Tennikova, Tatiana, Pešić, Milica, Krasavin, Mikhail, "Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential." in European Journal of Medicinal Chemistry, 191 (2020):112119,
https://doi.org/10.1016/j.ejmech.2020.112119 . .

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 .

TY  - JOUR
AU  - Jovanović, Mirna
AU  - Zhukovsky, Daniil
AU  - Podolski-Renić, Ana
AU  - Domračeva, Ilona
AU  - Žalubovskis, Raivis
AU  - Senćanski, Milan
AU  - Glišić, Sanja
AU  - Sharoyko, Vladimir
AU  - Tennikova, Tatiana
AU  - Dar'in, Dmitry
AU  - Pešić, Milica
AU  - Krasavin, Mikhail
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0223523419307147?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3488
AB  - A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate. Based on this initial screening, six compounds were selected for testing against recombinant rat TrxR1 and in the insulin assay to reveal low-micromolar to submicromolar potency of these inhibitors. The same frontrunner compounds were evaluated for their ability to exert antiproliferative activity and induce cell death and this activity was compared to the UMA effects on the levels of reactive oxygen and nitrogen species (RONS). Collectively, the UMA compounds class presented itself as a rich source of leads for TrxR1 inhibitor discovery for anticancer application. Compound 7 (DVD-445) was nominated a lead for further optimization.
T2  - European Journal of Medicinal Chemistry
T1  - Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy.
VL  - 181
DO  - 10.1016/j.ejmech.2019.111580
SP  - 111580
ER  - 

@article{
author = "Jovanović, Mirna and Zhukovsky, Daniil and Podolski-Renić, Ana and Domračeva, Ilona and Žalubovskis, Raivis and Senćanski, Milan and Glišić, Sanja and Sharoyko, Vladimir and Tennikova, Tatiana and Dar'in, Dmitry and Pešić, Milica and Krasavin, Mikhail",
year = "2019",
abstract = "A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate. Based on this initial screening, six compounds were selected for testing against recombinant rat TrxR1 and in the insulin assay to reveal low-micromolar to submicromolar potency of these inhibitors. The same frontrunner compounds were evaluated for their ability to exert antiproliferative activity and induce cell death and this activity was compared to the UMA effects on the levels of reactive oxygen and nitrogen species (RONS). Collectively, the UMA compounds class presented itself as a rich source of leads for TrxR1 inhibitor discovery for anticancer application. Compound 7 (DVD-445) was nominated a lead for further optimization.",
journal = "European Journal of Medicinal Chemistry",
title = "Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy.",
volume = "181",
doi = "10.1016/j.ejmech.2019.111580",
pages = "111580"
}

Jovanović, M., Zhukovsky, D., Podolski-Renić, A., Domračeva, I., Žalubovskis, R., Senćanski, M., Glišić, S., Sharoyko, V., Tennikova, T., Dar'in, D., Pešić, M.,& Krasavin, M.. (2019). Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy.. in European Journal of Medicinal Chemistry, 181, 111580.
https://doi.org/10.1016/j.ejmech.2019.111580

Jovanović M, Zhukovsky D, Podolski-Renić A, Domračeva I, Žalubovskis R, Senćanski M, Glišić S, Sharoyko V, Tennikova T, Dar'in D, Pešić M, Krasavin M. Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy.. in European Journal of Medicinal Chemistry. 2019;181:111580.
doi:10.1016/j.ejmech.2019.111580 .

Jovanović, Mirna, Zhukovsky, Daniil, Podolski-Renić, Ana, Domračeva, Ilona, Žalubovskis, Raivis, Senćanski, Milan, Glišić, Sanja, Sharoyko, Vladimir, Tennikova, Tatiana, Dar'in, Dmitry, Pešić, Milica, Krasavin, Mikhail, "Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy." in European Journal of Medicinal Chemistry, 181 (2019):111580,
https://doi.org/10.1016/j.ejmech.2019.111580 . .

TY  - JOUR
AU  - Bakulina, Olga
AU  - Bannykh, Anton
AU  - Jovanović, Mirna
AU  - Domračeva, Ilona
AU  - Podolski-Renić, Ana
AU  - Žalubovskis, Raivis
AU  - Pešić, Milica
AU  - Dar'in, Dmitry
AU  - Krasavin, Mikhail
PY  - 2019
UR  - https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1575372
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6374954
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3266
AB  - Human thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing enzyme which plays a crucial role in regulating numerous redox signalling pathways within the cell. While its functioning is important in all cells, levels of TrxR1 expression are higher in cancer cells, possibly as an adaptation to much higher levels of reactive oxygen species and the need for more extensive DNA synthesis. This makes TrxR1 an attractive target for cancer therapy development. Inspired by the structure of disulphide compounds which have advanced through various stages of clinical development, we designed a series of dithiodiglycolic acid derivatives. These were prepared from respective thiol synthons using an iodine- or benzotriazolyl chloride-promoted oxidative disulphide bond formation. Inhibition of TrxR present in cell lysates from human neuroblastoma cells (SH-SY5Y) and rat liver cells indicated several compounds with a potential for TrxR inhibition. Some of these compounds were also tested for growth inhibition against two human cancer cell lines and normal human keratinocytes.
T2  - Journal of Enzyme Inhibition and Medicinal Chemistry
T1  - Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols.
IS  - 1
VL  - 34
DO  - 10.1080/14756366.2019.1575372
SP  - 665
EP  - 671
ER  - 

@article{
author = "Bakulina, Olga and Bannykh, Anton and Jovanović, Mirna and Domračeva, Ilona and Podolski-Renić, Ana and Žalubovskis, Raivis and Pešić, Milica and Dar'in, Dmitry and Krasavin, Mikhail",
year = "2019",
abstract = "Human thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing enzyme which plays a crucial role in regulating numerous redox signalling pathways within the cell. While its functioning is important in all cells, levels of TrxR1 expression are higher in cancer cells, possibly as an adaptation to much higher levels of reactive oxygen species and the need for more extensive DNA synthesis. This makes TrxR1 an attractive target for cancer therapy development. Inspired by the structure of disulphide compounds which have advanced through various stages of clinical development, we designed a series of dithiodiglycolic acid derivatives. These were prepared from respective thiol synthons using an iodine- or benzotriazolyl chloride-promoted oxidative disulphide bond formation. Inhibition of TrxR present in cell lysates from human neuroblastoma cells (SH-SY5Y) and rat liver cells indicated several compounds with a potential for TrxR inhibition. Some of these compounds were also tested for growth inhibition against two human cancer cell lines and normal human keratinocytes.",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
title = "Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols.",
number = "1",
volume = "34",
doi = "10.1080/14756366.2019.1575372",
pages = "665-671"
}

Bakulina, O., Bannykh, A., Jovanović, M., Domračeva, I., Podolski-Renić, A., Žalubovskis, R., Pešić, M., Dar'in, D.,& Krasavin, M.. (2019). Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols.. in Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 665-671.
https://doi.org/10.1080/14756366.2019.1575372

Bakulina O, Bannykh A, Jovanović M, Domračeva I, Podolski-Renić A, Žalubovskis R, Pešić M, Dar'in D, Krasavin M. Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols.. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2019;34(1):665-671.
doi:10.1080/14756366.2019.1575372 .

Bakulina, Olga, Bannykh, Anton, Jovanović, Mirna, Domračeva, Ilona, Podolski-Renić, Ana, Žalubovskis, Raivis, Pešić, Milica, Dar'in, Dmitry, Krasavin, Mikhail, "Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols." in Journal of Enzyme Inhibition and Medicinal Chemistry, 34, no. 1 (2019):665-671,
https://doi.org/10.1080/14756366.2019.1575372 . .