Synthesis and Antibacterial Activity of New Amide Derivatives of Pyrimidinediones

Abstract

A series of ten new pyrimidinedione derivatives (4a-j) was synthesized from a common scaffold, 1-(((benzyloxy) carbonyl)methyl)-1,2,3,4-tetrahydro-2,4-dioxopyrimidine-5-carboxylic acid (2). The compound (2) was subjected to acid– amine coupling with different amines 3(a-j). The coupling reaction was performed using HATU as a coupling reagent at room temperature for 3h using the base N-methylmorpholine and solvent DMF. The desired derivatives were obtained with good yields. The synthesized compound’s purity was determined by HPLC analytical techniques. The structures of the pyrimidinediones were analyzed by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance (1H NMR), 13C NMR, liquid chromatography–mass spectrometry, and Human Resource Management System data. All ten amide derivatives were tested for antibacterial efficacy using Staphylococcus aureus (Gram-positive strain bacteria) and Pseudomonas putida (Gram-negative strain bacteria). Compounds 4g as well as 4h showed significant antibacterial effectiveness, with good minimum inhibition concentration values. A molecular docking study was also performed with the protein 3FQO selected from the Protein Data Bank. The amide compounds 4g and 4h displayed good docking scores. The results of the in silico study complemented the antibacterial effectiveness of the two analogs 4g and 4h. The presence of electron donating groups in these target molecules may be attributed to their high efficacy.