Design, Synthesis, and Antioxidant/Antidiabetic Activity of Nucleic Acid Bases Bearing Fused N,S-Heterocyclic Phosphor Esters

• Published in: Journal of heterocyclic chemistry 2015-11, Vol.52 (6), p.1654-1662
• Main Authors: Abdou, Wafaa M., Kamel, Azza A., Khidre, Maha D.
• Format: Article
• Language: English
• Subjects: Antioxidants
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.2260

Reactions of unsaturated and saturated Wadsworth–Horner–Emmons reactants with N1‐ and N3‐allyl‐2‐thiouracils, under phase‐transfer catalysis conditions, resulted in the respective N‐bridged thiazolo‐, pyrrolo‐, and thiazino‐phosphor esters. Products were obtained via the regioselective attack of the Wadsworth–Horner–Emmons reagent on the allylic‐1′‐C in tandem of double bond migration processes, followed by a series of transformations. Synthesis of pyrimidin‐1(2H, or 6H)‐yl)but‐1‐ene‐1,1‐diyldiphosphonates was also described. On the basis of the prediction results (PASS program, Moscow, Russia; free available internet version of PASS 2009.1: http://www.ibmc.msk.ru/PASS), we further estimated the antioxidant and antidiabetic activities of the synthesized compounds. The results showed that all compounds cause moderate to good antidiabetic activities. However, the thiazolophosphonates exhibited the highest inhibitory antioxidant activity; nevertheless, the diphosphonates manifested the best protective effects against DNA damage induced by bleomycin. Biological testing confirmed the results of computational modeling.