Synthesis and antidiabetic/antioxidant properties of nucleobase-bearing phosphor ester motifs

• Published in: Monatshefte für Chemie Vol. 148; no. 12; pp. 2195 - 2210
• Main Authors: Abdou, Wafaa M., Kamel, Azza A., Shaddy, Abeer A.
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.12.2017; Springer Nature; Springer Nature B.V
• Subjects: Analytical Chemistry; Antioxidants; Ascorbic acid; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Correlation analysis; Derivatives; Free radicals; Glucose; Inorganic Chemistry; Inorganic salts; Organic Chemistry; Original Paper; Phosphines; Phosphonates; Physical Chemistry; Physical Sciences; Reagents; Science & Technology; Theoretical and Computational Chemistry; Allyl-2-thiouracils; Phosphorus(III) reagents; Fused pyrimidinone thiazaphosphinanes; Pyrimidinone-vinyl phosphonates; RELEVANT PHOSPHONATES; INHIBITION; ANALOGS; DERIVATIVES
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-017-2034-5

A variety of substituted pyrimidinone-vinyl phosphonates and fused 2-oxothiazaphosphinanes was synthesized and identified. The new derivatives were prepared from the application of P(III) reagents, dialkyl, trialkyl phosphites, and tris(dialkylamino)phosphines on N 1 - and N 3 -allyl-2-thiouracils under different reaction conditions. Vinyl phosphonates were assigned Z -configuration according to the spectroscopic analysis. Eight vinyl phosphonates and seven fused 2-oxothiazaphosphinanes were screened for their antidiabetic and antioxidant activities. Three vinyl phosphonates exhibited antidiabetic and radical scavenging activities greater than the standard drugs glibenclamide and ascorbic acid, whereas another two vinyl derivatives displayed potencies almost equal to the standard drugs. Results of the screening also revealed a positive correlation between the two studied activities. Based on these observations, we could conclude that amelioration of the blood glucose levels leads to a decrease in the formation of free radicals and an attenuation of lipid peroxidation. Graphical abstract