In this study, a series of 7-chloro-3-(substituted benzylidene/phenyl ethylidene amino)-2-phenyl quinazolin-4(3H)-ones (1–10) were prepared and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB). The antitubercular screening results indicated that 7-chloro-3-(4-(dimethylamino)benzylidene amino)-2 phenylquinazolin-4(3H)-one (10) was the most potent one (MIC = 0.78 9 10-3 lM) and exhibited activity equivalent to the standard compound isoniazid (MIC = 0.80 9 10-3 lM). Further, the synthesized compounds were tested for their antibacterial activity against Gram positive and Gram negative bacteria. The comparison of antibacterial and antimycobacterial results indicated that different structural requirements are necessary for a compound to be effective against bacterial and mycobacterial targets.