Dithiadiazole derivative 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide-Novel modulator of store-operated calcium entry

Pathological calcium homeostasis accompanies the development of a large number of different diseases, therefore, the search for new modulators of calcium signaling remains highly actual. Last decades storeoperated calcium channels have been repeatedly postulated as a therapeutic target, so the compounds acting on them can be considered promising drug prototypes. Here, we tested several derivatives of 1,2,3,4-dithiadiazole, 1,3-thiazine, pyrazolopyrimidine and thiohydrazides for the ability to affect the thapsigargin-induced calcium response. Using calcium imaging and the patch-clamp technique we found that dithiadiazole derivative3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxidehad a strong inhibitory effect on store-operated calcium entry at the micromolar concentration in HEK293 cells. Moreover, incubation of the cells with this compound also resulted in the decrease of ER calcium content. Thus, we have postulated 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide as a novel inhibitor of store-operated calcium entry and suggested the derivatives of 1,2,3,4-dithiadiazole as a prospective class of compounds for searching new calcium modulators. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study tested a series of compounds with potential drug prototypes for their effects on calcium signaling. The results showed that one compound had a strong inhibitory effect and resulted in a decrease in ER calcium content. Therefore, this compound is considered a novel inhibitor of store-operated calcium entry.