Exploring 2,4-Disubstituted Pyrimidines as Antioxidant Agents: Synthesis, Drug-Like Properties, and Molecular Docking...

Grounded on the significance of pyrimidines as antibacterial, anticancer, antiviral, and antioxidant activities and in continuation of our work on pyrimidines as anti-inflammatory and antiviral agents, here reporting the synthesis of pyrimidine analogs 3(a-c) and 4(a,b). The structure of purified compounds was confirmed using spectral techniques such as IR, NMR, and mass spectra. These compounds were docked with horse heart cytochrome c (1hrc) and the SARS-CoV-2 enzyme (7t9l) to find their binding interaction with the mentioned proteins. Furthermore, drug-like properties of potent compounds were studied using SWISS ADME. Among the synthesized compounds, molecular docking studies of 3a and 4a have shown binding affinities of -8.9 and -9.0 kcal/mol for 1hrc higher than bioactive small molecule embelin, which has a binding affinity of -7.4 kcal/mol. For the SARS-CoV-2 enzyme (7t9l), the binding affinity of 3a and 4a were -7.4 and -7.2 kcal/mol compared to the pyrazole compound, which has a binding affinity of -6.3 kcal/mol. Based on the results, compounds were further screened for antioxidant potential using the DPPH method. However, the antioxidant activity of these two compounds is comparable to that of embelin and pyrazole analogs.