A series of novel N-(substituted)-2-[4-oxo-2-phenylquinazolin-3(4H)-yl] acetohydrazide derivatives were designed and synthesized, and their structures were characterized by 1H, 13C NMR, IR and Mass Spectral analysis. Their antimicrobial activity against bacterial strains and unicellular and multicellular pathogenic fungal strains were evaluated, and the results of in vitro antimicrobial evaluations of all newly synthesized compounds revealed that compounds 4(a-g) found to possess varied degree of antibacterial and antifungal activities Therefore, it can be inferred that presence of Schiff base nucleus in newly synthesized compounds can act as better system for antimicrobial activity. Lipinski rule were evident that all synthesized compounds have a good potential for development as an oral agent and can be potentially active drug candidate.