Keeping the objective to build up a new structural class of potent antimicrobials and antituberculosis agents, a series of potentially active quinoline-based azetidinone and thiazolidinone analogues has been synthesized by a simple and efficient synthetic protocol. The thione nucleus formed from 2-chloroquinoline-3-carbaldehyde using sodium sulphide in DMF followed by reaction with various substituted amine to form the corresponding Schiff base intermediates. Attempt has been made to derive final azetidinone and thiazolidinone analogues from Schiff bases by using chloroacetyl chloride and 2-mercapto acetic acid, respectively. Newer analogues were characterized by IR, 1 H NMR, 13C NMR spectroscopy and elemental analyses. The newly synthesized analogues were then examined for their antimicrobial activity against some bacterial and fungal strains as two Gram -ve bacteria (Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 741), two Gram ?ve bacteria (Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 430) and two fungal species (Aspergillus niger MTCC 282, Candida albicans MTCC 183) to develop a novel class of antimicrobial agents and The final compounds were tested for in vitro antituberculosis activity against Mycobacterium tuberculosis. Streptomycin, Isoniazid, Rifampicin and Ethambutol were used as standards in this test. These observations provide some predictions to design further antibacterial and antituberculosis active compounds prior to their synthesis according to molecular modeling studies.