Design, synthesis and antioxidant studies of thiopyrimidine-based Passerini reaction: sulfur linked derivatives

Researchers have shown that sulfur-based heterocyclic frameworks form the backbone of a wide variety of synthetic analogues with a wide variety of medicinal actions. In this study, Passerini 3-component condensation reaction (P-3-CCR) approach has been used for the design strategy for imparting sulfur-based starting material, synthesis and antioxidant potential of sulfur containing pyrimidine (α-acyloxy amide) derivatives. The thorough assessment of antioxidant activities with a reference drug allows a proficient assessment of the structure–activity relationships (SARs) of the diversely synthesized molecules of the series. Compounds 4f with 3,4-(OMe)₂ [17.35 ± 0.14 µM] and 4h with 4-NO₂ [19.21 ± 0.14 µM] functionalities were identified as lead scaffolds with minimum IC₅₀ values. A molecular docking investigation was also performed to compute the binding free energy of 4h and 4f to 1F9G. The results revealed a strong binding affinity (-7.1 kcal/mol) of both compounds as compared to that of ascorbic acid (-6.2 kcal/mol). A design strategy though molecular docking followed by MCRs approach to identify new α-acyloxy amides provided an outstanding approximation and shedded light on the sites of binding for their better use in medicinal field.