Zhang, Huifang M. published the artcileAntiviral Activity of an Isatin Derivative via Induction of PERK-Nrf2-Mediated Suppression of Cap-Independent Translation, Synthetic Route of 612-13-5, the publication is ACS Chemical Biology (2014), 9(4), 1015-1024, database is CAplus and MEDLINE.
The authors report an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds Treatment of cells with ID45 before or after infection significantly reduced viral particle formation, resulting in protection of cells from virus-induced apoptosis. In addition, ID45 treatment caused remarkable up-regulation of glucose-regulated protein 78 (GRP78), a hallmark of endoplasmic reticulum (ER) stress and an indicator of enhanced cell viability. In identifying the ER stress response pathway induced by ID45, the authors found that ID45 activated PKR-like ER protein kinase (PERK) but failed to up-regulate eIF2α phosphorylation. Instead ID45 activated transcription factor Nrf2 (NF-E2-related factor-2), which is evidenced by its nuclear translocation and upregulation of its downstream target genes NQO1 (NAD(P)H quinone-oxidoreductase 1) and GCLM (glutamate-cysteine ligase, modifier subunit). This observation was further verified by using siRNAs of GRP78 or Nrf2, which blocked both the translocation of Nrf2 and up-regulation of its target genes, leading to aggressive viral replication and enhanced cell apoptosis. Finally, the authors found that ID45-induced up-regulation of NQO1 protected eIF4GI, a eukaryotic cap-dependent translation initiation factor, from cleavage by CVB3 protease and degradation by proteasomes. Taken together, the authors’ findings established that a novel antiviral mechanism of isatin derivative ID45 inhibits CVB3 replication by promoting cell survival through a PERK/Nrf2-dependent ER stress pathway, which benefits host cap-dependent translation but suppresses CVB3 cap-independent translation.
ACS Chemical Biology published new progress about 612-13-5. 612-13-5 belongs to nitriles-buliding-blocks, auxiliary class Organic Pigment, name is 2-(Chloromethyl)benzonitrile, and the molecular formula is C15H14O3, Synthetic Route of 612-13-5.
Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts