1,2,3,4-dithiadiazole derivatives as a novel class of calcium signaling modulators. / Новикова, Ю.В. ; Грехнёв, Дмитрий Александрович; Ошколова, Арина; Номеровская, М.А.; Колесников, Д.О.; Крисанова, А.В. ; Ясковец, В.Н.; Чернов, Н.М.; Яковлев, И.П.; Казначеева, Елена Валентиновна; Вигонт, Владимир Александрович .
In: Biochemical and Biophysical Research Communications, Vol. 691, 149333, 08.01.2024.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - 1,2,3,4-dithiadiazole derivatives as a novel class of calcium signaling modulators
AU - Новикова, Ю.В.
AU - Грехнёв, Дмитрий Александрович
AU - Ошколова, Арина
AU - Номеровская, М.А.
AU - Колесников, Д.О.
AU - Крисанова, А.В.
AU - Ясковец, В.Н.
AU - Чернов, Н.М.
AU - Яковлев, И.П.
AU - Казначеева, Елена Валентиновна
AU - Вигонт, Владимир Александрович
PY - 2024/1/8
Y1 - 2024/1/8
N2 - Aberrant calcium signaling is associated with a diverse range of pathologies, including cardiovascular and neurodegenerative diseases, diabetes, cancer, etc… So, therapeutic strategies based on the correction of pathological calcium signaling are becoming extremely in demand. Thus, the development of novel calcium signaling modulators remains highly actual. Previously we found that 1,2,3,4-dithiadiazole derivative 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide can strongly reduce calcium uptake through store-operated calcium (SOC) channels. Here we tested several structurally related compounds and found that most of them can effectively affect SOC channels and attenuate calcium content in the endoplasmic reticulum, thus, establishing 1,2,3,4-dithiadiazoles as a novel class of SOC channel inhibitors. Comparing different 1,2,3,4-dithiadiazole derivatives we showed that previously published 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide and newly tested 3-(3,5-difluorophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole 2-oxide demonstrated the highest efficacy of SOC entry reduction, supposing the important role of electron-withdrawing substituents to realize the inhibitory activity of 1,2,3,4-dithiadiazoles.
AB - Aberrant calcium signaling is associated with a diverse range of pathologies, including cardiovascular and neurodegenerative diseases, diabetes, cancer, etc… So, therapeutic strategies based on the correction of pathological calcium signaling are becoming extremely in demand. Thus, the development of novel calcium signaling modulators remains highly actual. Previously we found that 1,2,3,4-dithiadiazole derivative 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide can strongly reduce calcium uptake through store-operated calcium (SOC) channels. Here we tested several structurally related compounds and found that most of them can effectively affect SOC channels and attenuate calcium content in the endoplasmic reticulum, thus, establishing 1,2,3,4-dithiadiazoles as a novel class of SOC channel inhibitors. Comparing different 1,2,3,4-dithiadiazole derivatives we showed that previously published 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide and newly tested 3-(3,5-difluorophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole 2-oxide demonstrated the highest efficacy of SOC entry reduction, supposing the important role of electron-withdrawing substituents to realize the inhibitory activity of 1,2,3,4-dithiadiazoles.
KW - Calcium signaling
KW - Dithiadiazole derivatives
KW - Ion channels
KW - Patch-clamp
KW - Store-operated calcium entry
UR - https://www.mendeley.com/catalogue/e038f112-5010-3f32-a0e6-079d12481d3e/
U2 - 10.1016/j.bbrc.2023.149333
DO - 10.1016/j.bbrc.2023.149333
M3 - Article
VL - 691
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
M1 - 149333
ER -
ID: 116160493