Chemistry is an experimental science, and the best way to enjoy it and learn about it is performing experiments.Introducing a new discovery about188614-01-9., Safety of Methyl 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate
Discovery of a Plasmodium falciparum Glucose-6-phosphate Dehydrogenase 6-phosphogluconolactonase Inhibitor (R,Z)-N-((1-Ethylpyrrolidin-2-yl)methyl)-2- (2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro
A high-throughput screen of the NIH’s MLSMR collection of ?340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (Pf G6PD). PfG6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum, the bifunctional enzyme glucose-6-phosphate dehydrogenase-6- phosphogluconolactonase (Pf GluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of PfGluPho. The lead compound identified from this effort, (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2- fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carbox-amide, 11 (ML276), is a submicromolar inhibitor of PfG6PD (IC50 = 889 nM). It is completely selective for the enzyme’s human isoform, displays micromolar potency (IC50 = 2.6 muM) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting Pf G6PD in vivo are in progress.
Because enzymes can increase reaction rates by enormous factors and tend to be very specific, Safety of Methyl 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate, typically producing only a single product in quantitative yield, they are the focus of active research.you can also check out more blogs about Safety of Methyl 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate
Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem