Resistance to bacterial and fungal strains towards existing antimicrobial agents has become an increasing incietment for research and development of new molecules to guard them. Quinazoline ring system could be clubbed into many ring systems which lead to potent and highly active compounds. In this work, series of eighteen compounds were docked into the ecKAS III binding site (1HNJ, PDB ID) by using schrodinger software. Out of which, six derivatives showed highest glide score. A simple method has been developed for synthesis of six N'-(2-{[2-substituted phenyl)-2-oxoethyl]sulfanyl }quinazolin-4-yl) pyridine-4-carbohydrazide derivatives by condensing N'-(2-sulfanylquinazolin-4-yl)pyridine-4-carbohydrazide with substituted phenacyl bromides. The structures of these synthesized compounds of 5A series are confirmed by elemental analysis and spectral data. Screening of some selected compounds was carried out for antibacterial and antifungal activities by serial dilution method. The result of title compounds revealed that most of the compounds possess high to moderate activity against tested bacterial and fungal strains. Morever it indicates that, among the prepared compounds, 5A2 and 5A3 have higher inhibitory effect at MIC ranging from 0.4 to 12.5 μg/ml, while compounds 5A1 and 5A6 have moderate inhibitory effect with MIC between 12.5-50 μg/ml on the growth of gram positive bacterial strains. Especially, compounds 5A2 and 5A7 were found to be highly active against fungi at MIC 0.8 μg/ml each comparable with ciprofloxacin and fluconazole respectively. Molecular modeling studies have suggested probable inhibition mechanism making it the most potent antimicrobial agents in the series.