17718-67-1Relevant academic research and scientific papers
Enzymatic synthesis of a vitamin B6 precursor
Prlainovic, Nevena Z.,Bezbradica, Dejan I.,Knezevic-Jugovic, Zorica D.,Velickovic, Dusan V.,Mijin, Dusan Z.
, p. 1491 - 1501 (2013)
3-Cyano-4-(ethoxymethyl)-6-methyl-2-pyridone, an important precursor in the synthesis of vitamin B6, is obtained in the addition reaction between 2-cyanoacetamide and 1-ethoxy-2,4-pentanedione catalyzed by lipase from Candida rugosa (triacylglycerol acylhydrolases, EC 3.1.1.3). This work shows new experimental data and mathematical modeling of the lipase-catalyzed synthesis of 3-cyano-4-(ethoxymethyl)-6-methyl-2-pyridone. Kinetic measurements were performed at 50 °C with an enzyme concentration of 1.2 % w/v. The experimental results were fitted with two kinetic models: the ordered bi-ter and ping-pong bi-ter model, and the initial rates of the reaction were found to correlate best with the ping-pong bi-ter mechanism with inhibition by 2-cyanoacetamide. The obtained specificity constants indicated that lipase from C. rugosa had a higher affinity towards 1-ethoxy-2,4-pentanedione compared to 2-cyanoacetamide.
Discovery of novel pyrido-pyrrolidine hybrid compounds as alpha-glucosidase inhibitors and alternative agent for control of type 1 diabetes
Luthra, Tania,Banothu, Venkanna,Adepally, Uma,Kumar, Krishna,M, Swathi,Chakrabarti, Saikat,Maddi, Srinivas R.,Sen, Subhabrata
, (2020/01/11)
A new library of pyrido-pyrrolidine hybrid compounds were designed, developed and screened for their antidiabetic property with α-glucosidase. The design is based on preliminary screening of key fragments identified from literature reported α-glucosidase inhibitors and antidiabetic compounds. The most active fragments were stitched to provide a pyrido-pyrrolidine hybrid molecule as a new motif. A library of these compounds were synthesized and screened against a series of α-glycosidases. Subsequently, compound 3k was the most efficacious analog with IC50 of 0.56 μM. Photoluminescence study and circular dichroism experiments indicated that compound 3k modulates the primary and secondary structure of the enzyme. It successfully brings down the fasting blood glucose level for streptozotocin (STZ, 70 mg/kg, Intraperitoneal) induced type I diabetic male Sprague-Dawley rats (250–320 g). At lower concentration, compound 3k slightly stimulates proliferation of BRIN-BD11 (α-glucose responsive beta cells from rat pancreas islets that secretes insulin) cells.
Dihydrofuro[3,4-c]pyridinones as inhibitors of the cytolytic effects of the pore-forming glycoprotein perforin
Lena, Gersande,Trapani, Joseph A.,Sutton, Vivien R.,Ciccone, Annette,Browne, Kylie A.,Smyth, Mark J.,Denny, William A.,Spicer, Julie A.
experimental part, p. 7614 - 7624 (2009/12/07)
Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure-activity relationships around the core bicyclic thioxofuropyridinone and pendant furan ring. This resulted in the identification of a submicromolar inhibitor of the perforin-induced lysis of Jurkat T-lymphoma cells.
