Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols. / Bakulina, Olga; Bannykh, Anton; Jovanović, Mirna; Domračeva, Ilona; Podolski-Renić, Ana; Žalubovskis, Raivis; Pešić, Milica; Dar’in, Dmitry; Krasavin, Mikhail.
в: Journal of Enzyme Inhibition and Medicinal Chemistry, Том 34, № 1, 01.01.2019, стр. 665-671.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols
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 - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
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.
KW - anticancer activity
KW - disulphide inhibitors
KW - dithiodiglycolic acid
KW - TrxR
KW - RAT-LIVER
KW - SYSTEM
KW - MAMMALIAN THIOREDOXIN
KW - ASSAY
KW - THIOREDOXIN REDUCTASE
KW - SELENOCYSTEINE
KW - PROBE
KW - DISULFIDES
UR - http://www.scopus.com/inward/record.url?scp=85061406486&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/design-synthesis-biological-evaluation-novel-derivatives-dithiodiglycolic-acid-prepared-via-oxidativ
U2 - 10.1080/14756366.2019.1575372
DO - 10.1080/14756366.2019.1575372
M3 - Article
C2 - 30746961
AN - SCOPUS:85061406486
VL - 34
SP - 665
EP - 671
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
SN - 1475-6366
IS - 1
ER -
ID: 39059793