Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation was written by Upadhyay, Neha;Tilekar, Kalpana;Jansch, Niklas;Schweipert, Markus;Hess, Jessica D.;Henze Macias, Luca;Mrowka, Piotr;Aguilera, Renato J.;Choe, Jun-yong;Meyer-Almes, Franz-Josef;Ramaa, C. S.. And the article was included in Bioorganic Chemistry in 2020.Name: 3,4-Dibromoaniline This article mentions the following:
Among Class I and II HDACs, HDAC8 is one of the essential epigenetic players in cancer progression. Therefore, authors designed, synthesized, and purified novel compounds containing N-substituted thiazolidinediones I (Ar = C6H5, 2-FC6H4, pyridin-2-yl, etc.). Cell viability assay of all compounds on leukemic cell lines showed the cytotoxic potential of I (Ar = 2,3-FC6H3, 2-Cl,5CF3C6H3, 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl, 4-MeC6H4, benzo[d]thiazol-2-yl, 3,4-BrC6H3). In-vitro screening of different HDACs isoforms revealed that I (Ar = benzo[d]thiazol-2-yl) was the most potent and selective inhibitor for HDAC8 (IC50 – 9.3μM). Thermal shift anal. confirmed the binding of I (Ar = benzo[d]thiazol-2-yl) to HDAC8. In-vitro screening of I on the transport activity of GLUT1, 4, and 5 indicated that I (Ar = benzo[d]thiazol-2-yl) inhibited GLUT1 (IC50 – 28.2μM). Thiazolidinedione I (Ar = 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) and I (Ar = benzo[d]thiazol-2-yl) induced apoptotic cell death in CEM cells (55.19% and 60.97% resp.) and I (Ar = benzo[d]thiazol-2-yl) was less cytotoxic on normal WBCs (CC50 – 104.2μM) and human fibroblasts (HS27) (CC50 – 105.0μM). Thus, among these, compound I (Ar = benzo[d]thiazol-2-yl) was most promising HDAC8 inhibitor and cytotoxic on leukemic cells. Thus, I (Ar = benzo[d]thiazol-2-yl) could serve as a lead for further development of optimized mols. with enhanced selectivity and potency. In the experiment, the researchers used many compounds, for example, 3,4-Dibromoaniline (cas: 615-55-4Name: 3,4-Dibromoaniline).
3,4-Dibromoaniline (cas: 615-55-4) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. alpha-Bromoesters are employed in the Reformatsky reaction for the synthesis of beta-hydroxyesters. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Name: 3,4-Dibromoaniline
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary