Design, synthesis of quinolinyl Schiff bases and azetidinones as enoyl ACP-reductase inhibitors

Abstract

New series of quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehydes. In the reaction sequence, substituted acetanilides were cyclized to give 2-chloroquinoline-3-carbaldehydes 2a–d, which were transformed to 6a–d, which were then cyclized to give azetidinones 9a–d. The key scaffolds viz., 2-methoxy derivatives 3a–d, obtained from 2a–d were converted to target Schiff bases 4a–d, 5a–d and azetidinones 7a–d, 8a–d in good yields. Structures of these compounds were established by FTIR, 1H NMR, 13C NMR and mass spectrometry. The compounds 4a–d to 9a–d were evaluated for in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Vibrio cholera and antitubercular activity against Mycobacterium tuberculosis H37Rv. The Schiff bases and azetidinone derivatives exhibited good antibacterial and antitubercular activities. Bacterial enoyl ACP-reductase catalyzes the final step in each cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antimicrobial agents. Molecular docking into active site of enoyl ACP-reductase was performed on 2H7M.PDB and 4JX8.PDB files to understand ligand–protein interactions. The compounds obtained from the present research can be used as scaffolds in fragment-based design of new potent drugs. Molecular modeling, synthesis, spectral, antimicrobial studies of quinolinyl Schiff bases and azetidinones using crystal structure of E. coli and M. tuberculosis enoyl ACP-reductase (4JX8/2H7M PDB) and compared with in vitro antimicrobial activity.