HDAC4 Inhibitors with Cyclic Linker and Non-hydroxamate Zinc Binding Group: Design, Synthesis, HDAC Screening and in vitro Cytotoxicity evaluation. was written by Tilekar, Kalpana;Hess, Jessica D.;Upadhyay, Neha;Schweipert, Markus;Flath, Felix;Gutierrez, Denisse A.;Loiodice, Fulvio;Lavecchia, Antonio;Meyer-Almes, Franz-Josef;Aguilera, Renato J.;Ramaa, C. S.. And the article was included in ChemistrySelect in 2021.Application of 615-55-4 This article mentions the following:
Recent evidences highlight the usefulness of small mol. (Histone deacetylase 4) HDAC4 inhibitors in the several preclin. paradigms. Major toxicity and mutagenicity issues associated with hydroxamate HDAC inhibitors, stimulated us to develop potent non-hydroxamate inhibitors. In the present work a novel series of thiazolidinedione (TZD) derivatives with pyridine as cyclic linker and TZD ring as zinc binding group was designed and screened in a panel of isoenzymes of HDACs, wherein the most potent compounds exhibiting HDAC4 IC50-values<5 μM were 5 v, 5 w, 5 y and 5 z (IC50=4.2±1 μM, 0.75±0.03 μM, 4.9±0.5 and 2.3±0.5 μM, resp.). The docking studies displayed the unique binding mode of this series of compound at active site of HDAC4, wherein TZD ring was indicated as zinc binding group. Further, 5 w and 5 y were found as the most potent antiproliferative agent in lymphoblastic leukemia (CCRF-CEM) and breast cancer MDA-MB-231 cells. Compound 5 y was found to induce the apoptosis and DNA fragmentation of CEM cells. The western blotting anal. of 5 y also showed the presence of cleaved caspases supporting their apoptotic nature. Further, Class IIa (HDAC4) selectivity of 5 y was also supported by western blotting observations, wherein 5 y caused the accumulation of acetylated H3 but not of acetylated Tubulin. Thus, our findings endorse the further investigation of this series of compounds for their potential as targeted cancer therapeutic agents. In the experiment, the researchers used many compounds, for example, 3,4-Dibromoaniline (cas: 615-55-4Application of 615-55-4).
3,4-Dibromoaniline (cas: 615-55-4) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Application of 615-55-4
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary