Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma mansoni (SmSirt2) was written by Monaldi, Daria;Rotili, Dante;Lancelot, Julien;Marek, Martin;Woessner, Nathalie;Lucidi, Alessia;Tomaselli, Daniela;Ramos-Morales, Elizabeth;Romier, Christophe;Pierce, Raymond J.;Mai, Antonello;Jung, Manfred. And the article was included in Journal of Medicinal Chemistry in 2019.Computed Properties of C13H12O2 The following contents are mentioned in the article:
The only drug currently available for treatment of the neglected disease Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary and urgent. To this end, the targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as a promising approach. Due to the strong effects of human sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as potential therapeutic targets. In vitro testing of synthetic substrates of S. mansoni sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long-chain deacylation as an intrinsic SmSirt2 activity in addition to its known deacetylase activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships of identified hits led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Computed Properties of C13H12O2).
4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Computed Properties of C13H12O2
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem