Design, Synthesis, and biological evaluation of 8-mercapto-3,7-dihydro-1H-purine-2,6-diones as potent inhibitors of SIRT1, SIRT2, SIRT3, and SIRT5 was written by Han, Haozhen;Li, Chunpu;Li, Man;Yang, Lisheng;Zhao, Sen;Wang, Zhifei;Liu, Hong;Liu, Dongxiang. And the article was included in Molecules in 2020.Computed Properties of C9H11BrO This article mentions the following:
Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases. They regulate many physiol. processes and play important roles in inflammation, diabetes, cancers, and neurodegeneration diseases. Sirtuin inhibitors have potential applications in the treatment of neurodegenerative diseases and various cancers. Herein, we identified new sirtuin inhibitors based on the scaffold of 8-mercapto-3,7-dihydro-1H-purine-2,6-dione. To elucidate the inhibitory mechanism, the binding modes of the inhibitors in SIRT3 were established by mol. docking, showing that the inhibitors occupy the acetyl lysine binding site and interact with SIRT3, mainly through hydrophobic interactions. The interactions were validated by site-directed mutagenesis of SIRT3 and structure-activity relationship anal. of the inhibitors. Consistently, enzyme kinetic assays and microscale thermophoresis showed that these compounds are competitive inhibitors to the acetyl substrate, and mix-type inhibitors to NAD+. Furthermore, we demonstrated that the compounds are potent SIRT1/2/3/5 pan-inhibitors. This study provides novel hits for developing more potent sirtuin inhibitors. In the experiment, the researchers used many compounds, for example, 1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0Computed Properties of C9H11BrO).
1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon–bromine bond is electrophilic in nature. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.Computed Properties of C9H11BrO
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary