Supramolecular beta-cyclodextrin as a highly efficient, biodegradable, and reusable catalyst for the synthesis of 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carbonitrile derivatives (4a-s) is investigated via a cascade reaction of aldehydes, malanonitrile and 2-aminopyridine in aqueous medium at 65 A degrees C under ultrasonication. This procedure has the advantages of good yields, easy work-up, and benign environment friendly character. All of the synthesized derivatives were evaluated for their in vitro antibacterial activity against four bacterial strains.