Design, Synthesis, Characterization, and Study of in vitro Antioxidant Activity of Some Substituted Biginelli Derivatives

The Biginelli class of 3,4-dihydropyrimidinone (DHPM) or its thione (DHPMT) derivatives can act as an exciting pharmacophoric moiety, which in turn has attracted the extensive attention of medicinal chemists in the last few decades. Similarly, imidazolidin-4-one also occupies an inevitable place in drug discovery chemistry. Despite numerous diverse pharmacologic effects ascribed to these two derivatives together being reported, there are few reports on the antioxidant evaluation of the Biginelli class of pyrimidinone derivatives annexed to imidazolidinone by an amide bond. In this study, the synthesis of 20 novel 3,4-dihydropyrimidinones with imidazolidin-4-one derivatives is described. The physical characteristics of the synthesized 3,4-DHPM and DHPMT derivatives were determined and analytically characterized by various spectral tools like FT-IR, Lc-Ms/Ms, and proton and carbon NMR. The scavenging radical potential for the synthesized 20 novel Biginelli derivatives was assessed using the DPPH assay. The results indicated that all the tested compounds had good to excellent antioxidant potency in comparison to the standard drug ascorbic acid. The synthesized compounds 1, 6, 8, 9, 14, 15, 16, 17, 18, and 19 showed a good degree of scavenging potency. Interestingly, remarkable activity was observed with compounds 16, 17, and 19. The present study reveals that not only the compounds with an OH group can exhibit a high degree of scavenging potency, but other groups like -OCH3, –CH3, and -Cl can also exhibit activity effectively. In addition, the radical scavenging potential for the studied compounds could be due to either the presence of more than one labile hydrogen atom attached to a nitrogen atom or the conjugated system, i.e. the 3,4-dihydropyrimidinone ring attached to an amide linkage, present in these compounds, which would have further sponsored the compound to get stabilized when these compounds become radicals by donating an electron to ROS.