In an effort to discover new candidates with improved antimicrobial activities, we synthesized and studied invitro antimicrobial activities of various series of 3-((thiophen-2-yl)-ethyl)-2-(styryl)-quinazolin-4(3H)-one (3a-3g) and N1-(substituted aryl)-N3-[3-((3,4-dimethoxy phenyl-2-yl)-ethyl)-4(3H)-quinazolone-2-yl]-acetonyl semicarbazides (7a-7j) with an intent to overcome multiple drug resistance to the pathogenic strains and to retain psychological action to develop novel class of antibacterial agents. The structure of newly synthesized scaffolds has been affirmed on the basis of FTIR, 1H NMR, 13C NMR, mass and elemental analysis. All the final scaffolds have been subjected to in vitro antimicrobial screening against two Gram (+Ve) bacteria (S. aureus, B. subtilis), two Gram (-Ve) bacteria (E. coli, S.typhi) and two fungal strains (C. albicans, A. niger) using the broth micro-dilution method.