Synthesis, Molecular Docking and Pharmacological Study of Pyrimidothiadiazinones and its bis-derivatives

Background: A series of pyrimidothiadiazinones 5a-n were prepared from aminomethylation of pyrimidinethione 1 with different primary amines and formaldehyde through Mannich reaction. The spectral data of the formed products confirmed the suggested structures. Method: Most of the newly synthesized compounds were tested for their antimicrobial and anticancer activities. Depending on the obtained results, the newly synthesized compounds possess good to moderate activities. Compound 5e exhibited the highest antibacterial activity measured in 22.1, 18.6, 17.2 and 16.8 mm against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa, respectively. Compound 5e exhibited highest potency with MIC values of 125, 250, 250, and 500 μg/mL against E. coli, S. aureus, B. subtilis, and P. aureginosa, respectively. Results: Compound 5j exhibited the highest inhibitory effect against breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG2) cell lines. Also, molecular docking against E. Coli Enoyl Reductase; PDB ID (1LXC) and Human Dihydrofolate Reductase; PDB ID (1DLS) revealed high free binding energy and good binding mode. The structure activity relationship (SAR) of tested compounds was also studied.