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.