ORIGINAL RESEARCH Design, synthesis of quinolinyl Schiff bases and azetidinones as enoyl ACP-reductase inhibitors Shrinivas D. Joshi 1 • Uttam A. More 1,2 • Deepak Parkale 1 • Tejraj M. Aminabhavi 1 • Andanappa K. Gadad 3 • Mallikarjuna N. Nadagouda 1 • Rahul Jawarkar 4 Received: 3 July 2014 / Accepted: 17 August 2015 Ó Springer Science+Business Media New York 2015 Abstract New series of quinoline derivatives were syn- thesized 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 aze- tidinones 9a–d. The key scaffolds viz., 2-methoxy deriva- tives 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, 1 H NMR, 13 C NMR and mass spectrometry. The compounds 4a–d to 9a–d were evaluated for in vitro antibacterial activity against Staphylococcus aureus, Bacil- lus subtilis, Escherichia coli and Vibrio cholera and antitu- bercular activity against Mycobacterium tuberculosis H 37 Rv. 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. Graphical Abstract 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. Keywords Quinolines  Pyrroles  Schiff bases  Antibacterial activity  Antitubercular activity  Surflex-Dock Introduction Tuberculosis (TB), is a communicable disease, spreads through air and caused by the bacterium Mycobacterium tuberculosis (MTB), is regarded as a serious global prob- lem. According to statistics, about one-third of the world’s population is infected with TB affecting nearly 8 million This paper is affectionately dedicated to my teacher Dr. V. H. Kulkarni for his service to Pharmacy Profession. & Shrinivas D. Joshi shrinivasdj@rediffmail.com 1 Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad, Karnataka 580 002, India 2 Centre for Research and Development, Prist University, Thanjavur, Tamil Nadu 613 403, India 3 School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Champs-Fleurs, Mount-Hope, Trinidad and Tobago 4 Department of Pharmaceutical Chemistry, Sahyadri College of Pharmacy, Methawade, Sangola, Maharashtra 413 307, India 123 Med Chem Res DOI 10.1007/s00044-015-1432-7 MEDICINAL CHEMISTRY RESEARCH