Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols
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 t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1575372 |
| _version_ | 1819038517757476864 |
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| author | Olga Bakulina Anton Bannykh Mirna Jovanović Ilona Domračeva Ana Podolski-Renić Raivis Žalubovskis Milica Pešić Dmitry Dar’in Mikhail Krasavin |
| author_facet | Olga Bakulina Anton Bannykh Mirna Jovanović Ilona Domračeva Ana Podolski-Renić Raivis Žalubovskis Milica Pešić Dmitry Dar’in Mikhail Krasavin |
| author_sort | Olga Bakulina |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T08:38:34Z |
| format | Article |
| id | doaj.art-56ccb2a5330943a7acddac380ac74b62 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-21T08:38:34Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-56ccb2a5330943a7acddac380ac74b622022-12-21T19:10:00ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-0134166567110.1080/14756366.2019.15753721575372Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiolsOlga Bakulina0Anton Bannykh1Mirna Jovanović2Ilona Domračeva3Ana Podolski-Renić4Raivis Žalubovskis5Milica Pešić6Dmitry Dar’in7Mikhail Krasavin8Saint Petersburg State UniversitySaint Petersburg State UniversityInstitute for Biological Research “Siniša Stanković”, University of BelgradeLatvian Institute of Organic SynthesisInstitute for Biological Research “Siniša Stanković”, University of BelgradeLatvian Institute of Organic SynthesisInstitute for Biological Research “Siniša Stanković”, University of BelgradeSaint Petersburg State UniversitySaint Petersburg State UniversityHuman 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.http://dx.doi.org/10.1080/14756366.2019.1575372trxrdisulphide inhibitorsdithiodiglycolic acidanticancer activity |
| spellingShingle | Olga Bakulina Anton Bannykh Mirna Jovanović Ilona Domračeva Ana Podolski-Renić Raivis Žalubovskis Milica Pešić Dmitry Dar’in Mikhail Krasavin Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols Journal of Enzyme Inhibition and Medicinal Chemistry trxr disulphide inhibitors dithiodiglycolic acid anticancer activity |
| title | Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols |
| title_full | Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols |
| title_fullStr | Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols |
| title_full_unstemmed | Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols |
| title_short | Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols |
| title_sort | design synthesis and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols |
| topic | trxr disulphide inhibitors dithiodiglycolic acid anticancer activity |
| url | http://dx.doi.org/10.1080/14756366.2019.1575372 |
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