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The present work describes an efficient and environmentally benign four component synthesis of structurally diverse substituted pyrido-pyrimidines involving the reaction of barbituric acid, 4-hydroxy 6-methyl 2-pyrone, an aromatic aldehyde and ammonium acetate in low transition temperature mixture (LTTM) (glycerol:proline: 1:1). The LTTM serves as green solvent which is an inexpensive, nontoxic and plays a dual function (reusable catalyst and solvent), and is found to be an excellent reaction endorsing medium. The present protocol offers some advantages such as easy work up, shorter reaction time, an excellent yield with higher atom economy, maximum reaction efficiency with an excellent green chemistry metrics. The synthesized compounds have been evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay as well as molecular docking studies performed on myeloperoxidase enzyme. Tested scaffolds exhibits an excellent results of virtual screening and antioxidant activity. [ABSTRACT FROM AUTHOR]