An Expedient Three-component Synthesis of Novel Pyrido-pyrimidine Derivatives: Antimicrobial Activity, Molecular Docking, and ADME Studies

A facile and efficient protocol for one-pot three-component synthesis of a series of novel 4-substituted-2-thioxo-3,4-dihydro-1H-pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5(2H)-one derivatives has been developed. Compounds were synthesized by the reaction of 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione, various aromatic aldehydes, and thiourea using Iodine as catalyst in acidic medium. The synthesized compounds obtained in good to excellent yields (52–83%) with improved reaction time and chloro substituent at four-position yielded the product in excellent quantity (83%). The synthesized compounds have been characterized by 1H, and 13C NMR, IR, and mass spectral analysis, and screened for their in vitro antibacterial activity against Bacillus subtilis, Salmonella typhemurium, Escherichia. coli, and Staphylococcus aureus using disk diffusion method. Biological screening revealed that the newly synthesized compounds exhibit interesting activities against several bacterial strains. Among all the synthesized compounds, the in vitro antibacterial activity displayed by compound 6j was highest against S. typhemurium with ZOI 23.5. mm (MIC = 3.125 µg/mL). Docking studies further supported the findings, and provided for the basis of linkages in terms of conventional hydrogen bonds, and pi- bonding patterns. In nutshell, the present study thus paved the way for developing lead compounds which could be potentially used as an efficient antibacterial drug in humans after appropriate animal, and clinical trials.