The systematic study of pyrimidines began in 1884 with Pinner, who synthesized derivatives by condensing ethyl acetoacetate with amidines. Pinner first proposed the name “pyrimidin” in 1885. 65-86-1, formula is C5H4N2O4, Name is 2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid. The parent compound was first prepared by Gabriel and Colman in 1900, by conversion of barbituric acid to 2,4,6-trichloropyrimidine followed by reduction using zinc dust in hot water. COA of Formula: C5H4N2O4.
Summers, Robert L.;Pasaje, Charisse Flerida A.;Pisco, Joao P.;Striepen, Josefine;Luth, Madeline R.;Kumpornsin, Krittikorn;Carpenter, Emma F.;Munro, Justin T.;Lin, De;Plater, Andrew;Punekar, Avinash S.;Shepherd, Andrew M.;Shepherd, Sharon M.;Vanaerschot, Manu;Murithi, James M.;Rubiano, Kelly;Akidil, Asli;Ottilie, Sabine;Mittal, Nimisha;Dilmore, A. Hazel;Won, Madalyn;Mandt, Rebecca E. K.;McGowen, Kerry;Owen, Edward;Walpole, Chris;Llinas, Manuel;Lee, Marcus C. S.;Winzeler, Elizabeth A.;Fidock, David A.;Gilbert, Ian H.;Wirth, Dyann F.;Niles, Jacquin C.;Baragana, Beatriz;Lukens, Amanda K. research published 《 Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention》, the research content is summarized as follows. We identify the Plasmodium falciparum acetyl-CoA synthetase (PfAcAS) as a druggable target, using genetic and chem. validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds In vitro biochem. assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 directly inhibit the enzyme by preventing CoA and acetate binding, resp. Immunolocalization studies reveal that PfAcAS is primarily localized to the nucleus. Functional studies demonstrate inhibition of histone acetylation in compound-treated wild-type, but not in resistant parasites. Our findings identify and validate PfAcAS as an essential, druggable target involved in the epigenetic regulation of gene expression.
65-86-1, Orotic acid anhydrous is a hydrogen bonding interaction that can be found in biological systems. It plays a role in the physiological effects of orotic acid, which is a metabolite of uridine and an intermediate in the synthesis of pyrimidine nucleotides. Orotic acid has antimicrobial properties and has been shown to inhibit enzyme activities involved in energy metabolism, such as polymerase chain reaction (PCR) and adenosine triphosphate (ATP) synthase. Orotic acid also inhibits the growth of bacteria, fungi, and parasites. Orotic acid anhydrous is used for treating myocardial infarcts or brain functions. The untreated group was given no treatment at all.
Orotic acid, also known as orotate or orotsaeure, belongs to the class of organic compounds known as pyrimidinecarboxylic acids. These are pyrimidines with a structure containing a carboxyl group attached to the pyrimidine ring. Orotic acid exists as a solid, slightly soluble (in water), and a moderately acidic compound (based on its pKa). Orotic acid has been found in human liver and pancreas tissues, and has also been primarily detected in saliva, feces, urine, and blood. Within the cell, orotic acid is primarily located in the cytoplasm and mitochondria. Orotic acid exists in all eukaryotes, ranging from yeast to humans. Orotic acid participates in a number of enzymatic reactions. In particular, Orotic acid can be biosynthesized from L-dihydroorotic acid and quinone; which is mediated by the enzyme dihydroorotate dehydrogenase (quinone), mitochondrial. In addition, Orotic acid and phosphoribosyl pyrophosphate can be converted into orotidylic acid through its interaction with the enzyme uridine monophosphate synthetase isoform a. In humans, orotic acid is involved in the pyrimidine metabolism pathway. Orotic acid is also involved in several metabolic disorders, some of which include the mngie (mitochondrial neurogastrointestinal encephalopathy) pathway, dihydropyrimidinase deficiency, UMP synthase deficiency (orotic aciduria), and Beta ureidopropionase deficiency. Outside of the human body, orotic acid can be found in a number of food items such as green vegetables, alaska blueberry, chickpea, and colorado pinyon. This makes orotic acid a potential biomarker for the consumption of these food products. Orotic acid is a potentially toxic compound. Orotic acid has been found to be associated with several diseases known as phosphoenolpyruvate carboxykinase deficiency 1, cytosolic and hyperornithinemia-hyperammonemia-homocitrullinuria; orotic acid has also been linked to several inborn metabolic disorders including n-acetylglutamate synthetase deficiency, lysinuric protein intolerance, and ornithine transcarbamylase deficiency.
Orotic acid appears as white crystals or crystalline powder.
Orotic acid is a pyrimidinemonocarboxylic acid that is uracil bearing a carboxy substituent at position C-6. It has a role as a metabolite, an Escherichia coli metabolite and a mouse metabolite. It derives from a uracil. It is a conjugate acid of an orotate., COA of Formula: C5H4N2O4
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia