Several novel 4-hydroxy-chromene-2-one derivatives 2b-16b were easily prepared through condensation reactions with microwave heating and characterized by elemental analysis, IR, (1)H-NMR and mass spectrometry. Geometry optimization of these compounds was executed by PM3, PM5 and Minimize Energy methods to describe them via molecular descriptors. The antimicrobial activity of the synthesized compounds was evaluated against different microbial strains using two different methods: the diffusion method and the micro-dilution method. All data indicated that the products possess antimicrobial activity which depends on the nature of substituent attached to the benzopyran moiety. In general, after 24 h the MIC values of most tested coumarins was 0.13 mg/mL, but compounds 1 and 6b displayed the strongest antimicrobial activity on the tested cultures of bacteria after 48 h. Compound 13b has the strongest growth inhibitory potential on fungus C. albicans, tested by diffusion method,with an inhibition zone of 30-37 mm at a concentration of 150 microg/mL. The conclusion of this experiment is that the synthesized compounds have varied and different influence on different classes of bacteria and the fungus C. albicans.