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
Нема приказа
Аутори
Jovanović, MirnaZhukovsky, Daniil
Podolski-Renić, Ana
Domračeva, Ilona
Žalubovskis, Raivis
Senćanski, Milan V.
Glišić, Sanja
Sharoyko, Vladimir
Tennikova, Tatiana
Dar'in, Dmitry
Pešić, Milica
Krasavin, Mikhail
Чланак у часопису (Објављена верзија)
,
© 2019 Elsevier Masson SAS
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Приказ свих података о документуАпстракт
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. © 2019 Elsevier Masson SAS
Извор:
European Journal of Medicinal Chemistry, 2019, 181, 111580-Финансирање / пројекти:
- Russian Foundation for Basic Research (RFBR) [18-515-76001]
- Идентификација молекуларних маркера за предикцију прогресије тумора, одговора на терапију и исхода болести (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- ERA.Net RUS plus joint program grant [RUS_ST2017-309]
- State Education Development Agency of Republic of Latvia ["THIOREDIN"]
- Short-Term Scientific Mission (STSM) Grant from COST Action "New diagnostic and therapeutic tools against multidrug resistant tumors" [CA17104]
- European Cooperation in Science and Technology (COST)
DOI: 10.1016/j.ejmech.2019.111580
ISSN: 0223-5234
PubMed: 31400708
WoS: 000493211900034
Scopus: 2-s2.0-85073183701
Колекције
Институција/група
VinčaTY - JOUR AU - Jovanović, Mirna AU - Zhukovsky, Daniil AU - Podolski-Renić, Ana AU - Domračeva, Ilona AU - Žalubovskis, Raivis AU - Senćanski, Milan V. AU - Glišić, Sanja AU - Sharoyko, Vladimir AU - Tennikova, Tatiana AU - Dar'in, Dmitry AU - Pešić, Milica AU - Krasavin, Mikhail PY - 2019 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8532 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. © 2019 Elsevier Masson SAS 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 SP - 111580 DO - 10.1016/j.ejmech.2019.111580 ER -
@article{ author = "Jovanović, Mirna and Zhukovsky, Daniil and Podolski-Renić, Ana and Domračeva, Ilona and Žalubovskis, Raivis and Senćanski, Milan V. 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. © 2019 Elsevier Masson SAS", 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", pages = "111580", doi = "10.1016/j.ejmech.2019.111580" }
Jovanović, M., Zhukovsky, D., Podolski-Renić, A., Domračeva, I., Žalubovskis, R., Senćanski, M. V., 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 MV, 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 V., 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 . .