Synthesis, antioxidant and antimicrobial activities, molecular docking study of new pyrimidine derivatives

Abstract

Organic compounds, especially heterocyclic compounds, are known for their significant bioactivity, in this work, novel pyrimidine derivatives 3-11 were synthesized from the reaction of chalcon compound 1 with hydrogen peroxide to give oxiran compound 2 which reacted with thiourea producing the precursor key compound 3. Elemental analysis and several spectroscopic techniques were used to determine the molecular structures of the novel derivatives. All the new analogs were screened against four human pathogenic microbial strains: Escherichia coli as Gram-negative bacteria, Bacillus subtilis as Gram-positive bacteria and the yeast Candida albicans and Aspergillus niger using agar diffusion method, suggesting broad-spectrum potential. whereas compounds 5, 9a and 11 exhibited high inhibitory action with an inhibition zone of 17-20 mm compared to standard drugs, Streptomycin and Cycloheximide. Antioxidant profile employing DPPH radical scavenging studies further proved their capacity to lower oxidative stress. Whereas compounds 5, 9a and 11 showed significant DPPH activity and antioxidant activities. Additionally, at doses of 2.0, 1.0, and 0.5 mg/ml, compounds 3, 4, 6a, 8 and 9b showed moderate antioxidant activity. Conversely, compounds 6b, 6c, 7 and 10 showed very little DPPH activity. Molecular docking tests revealed strong binding affinities with significant microbial enzymes, which corroborated these conclusions and were in line with their observed inhibitory effects. Complementary and drug-like in silico ADMET testing confirmed that Lipinski's recommendations were followed, showing that oral delivery was suitable. Some of the produced compounds showed good pharmacological activity when compared to reference controls. A comprehensive synthesis, spectroscopic analyses, and pharmacological activity were all reported.