BACKGROUND Replacement of chloride ions in cyanuric chloride give several variants of 1,3,5-triazine derivatives which were investigated as biologically active small molecules. These compounds exhibit antimalarial, antimicrobial, anti-cancer and anti-viral activities, among other beneficial properties. On the other hand, treatment of bacterial infections remains a challenging therapeutic problem because of the emerging infectious diseases and the increasing number of multidrug-resistant microbial pathogens. As multidrug-resistant bacterial strains proliferate, the necessity for effective therapy has stimulated research into the design and synthesis of novel antimicrobial molecules. RESULTS 1,3,5-Triazine 4-aminobenzoic acid derivatives were prepared by conventional method or by using microwave irradiation. Using microwave irradiation gave the desired products in less time, good yield and higher purity. Esterification of the 4-aminobenzoic acid moiety afforded methyl ester analogues. The s-triazine derivatives and their methyl ester analogues were fully characterized by FT-IR, NMR (1H-NMR and 13C-NMR), mass spectra and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activity. Some tested compounds showed promising activity against Staphylococcus aureus and Escherichia coli. CONCLUSIONS Three series of mono-, di- and trisubstituted s-triazine derivatives and their methyl ester analogues were synthesized and fully characterized. All the synthesized compounds were evaluated for their antimicrobial activity. Compounds (10), (16), (25) and (30) have antimicrobial activity against S. aureus comparable to that of ampicillin, while the activity of compound (13) is about 50% of that of ampicillin. Compounds (13) and (14) have antimicrobial activity against E. coli comparable to that of ampicillin, while the activity of compounds (9-12) and (15) is about 50% of that of ampicillin. Furthermore, minimum inhibitory concentrations values for clinical isolates of compounds (10), (13), (14), (16), (25) and (30) were measured. Compounds (10) and (13) were more active against MRSA and E. coli than ampicillin. Invitro cytotoxicity results revealed that compounds (10) and (13) were nontoxic up to 250 µg/mL (with SI = 10) and 125 µg/mL (with SI = 5), respectively. Graphical abstract Three series of mono-, di- and trisubstituted s-triazine derivatives and their methyl ester analogues were synthesized and evaluated for their antimicrobial activity. Several compounds have antimicrobial activity against S. aureus and E. coli comparable to that of ampicillin.