Design, Synthesis and Antimicrobial Activity of 1,3-Diazine Derivatives

Abstract

Background: Pyrimidines have been shown to possess numerous biological activities, such as antimicrobial, anticancer, anticonvulsant, antiviral, and anti-inflammatory. Objective: Encouraged by these data, the synthesis of 2-((1H-benzo[d]imidazol-2-yl)methylthio)-4- amino-6-phenylpyrimidine-5-carbonitrile (3a-g) was performed. Methods: 4-amino-2-mercapto-6-phenylpyrimidine-5-carbonitrile was dissolved in an aqueous sodium hydroxide solution, and to this clear solution, 2-chloromethyl-1H-benzimidazole in methanol was added, and the reaction mixture was stirred under reflux to get the desired product. The structures of the newly synthesized compounds were confirmed by their physical, chemical, and spectral data. The synthesized derivatives were screened for their in vitro antibacterial activity against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, by using ciprofloxacin as a reference standard. While, their antifungal activity was evaluated against Aspergillus niger and Candida albicans using fluconazole as a reference drug. The docking study was performed to check the interactions of target compounds (3a-g) with homo sapiens DHFR (PDB: 1S3V), bacterial (S. aureus) DHFR (PDB: 2W9T), and DHPS (PDB: 1AD4) protein. The dock score and binding interactions were recorded. Result: The antimicrobial activity study indicated compounds with chloro (3b), fluoro (3f), and bromo (3g) substituents to show good antibacterial as well as antifungal activity. The docking study revealed that the same compounds, i.e., 3b, 3f, and 3g, showed good dock score and comparable interactions compared to the reference ligand (trimethoprim/sulfadiazine), which confirmed their selectivity. Conclusion: It can be presumed that the synthesized compounds have the capability for further promotion as novel antimicrobial agents.