Molecular Docking, Multicomponent One-pot Synthesis of Pyrimidine Derivatives as Anti-mycobacterial Agents

Molecular docking study is used significantly in the drug discovery process for predicting the interaction between drug and receptor. This technique has been used commonly to identify the binding affinity and orientation of drug molecules at the binding site of the target. The main objectives of docking studies include accurate modeling of molecular structure and precise prediction of the biological activity of the drug molecules. Based on this concept, a series of 2-amino-6-(substituted phenyl)-4-oxo-4,5-dihydropyrimidine-5-carbonitrile derivatives have been designed and synthesized via multicomponent reaction. The synthetic protocol involves the one-pot, three-component reaction between equimolar quantities of substituted benzaldehydes, ethyl cyanoacetate, and guanidine in an ethanolic sodium hydroxide solution. The main objectives of docking studies include accurate modeling of molecular structure and precise prediction of biological activity of the drug molecules. The characterization of the titled compounds was carried out by assessing infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and mass spectrometry (MS) data. The synthesized compounds were screened for their in vitro anti-mycobacterial activity by using the luciferase reporter phage (LRP) assay method. The determination of anti-mycobacterial activity was carried out in terms of the percent reduction in the relative light unit (RLU). The test compounds displayed significant activity against Mycobacterium strain H37Rv in comparison to isoniazid as a standard drug.