Synthesis and mechanistic studies of 4-aminoquinoline-Isatin molecular hybrids and Schiff's bases as promising antimicrobial agents

Mohd Shakir; Asghar Ali; Swati Lakshmi; Manika Garg; Haider Thaer Abdulhameed Almuqdadi; Iram Irfan; Mohan Kamthan; Mukesh C Joshi; Saleem Javed; Diwan S Rawat; Mohammad Abid

doi:10.1016/j.ejmech.2024.117127

Synthesis and mechanistic studies of 4-aminoquinoline-Isatin molecular hybrids and Schiff's bases as promising antimicrobial agents

Eur J Med Chem. 2024 Dec 5:283:117127. doi: 10.1016/j.ejmech.2024.117127. Online ahead of print.

Authors

Affiliations

¹ Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India; Department of Chemistry, University of Delhi, Delhi, 110007, India.
² Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India; Clinical Biochemistry Lab, Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
³ Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
⁴ Clinical Biochemistry Lab, Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
⁵ Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India; Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, Iraq.
⁶ Department of Chemistry, Kirori Mal College, University of Delhi, Delhi, 110007, India.
⁷ Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
⁸ Department of Chemistry, University of Delhi, Delhi, 110007, India. Electronic address: dsrawat@chemistry.du.ac.in.
⁹ Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. Electronic address: mabid@jmi.ac.in.

PMID: 39673862
DOI: 10.1016/j.ejmech.2024.117127

Abstract

In this investigation, to determine their potential as specific antibacterial agents, Schiff's bases (LT-SB1-23 and SB1-SB12) and novel quinoline-isatin hybrids were subjected to microbiological testing. The in-vitro screening against bacterial strains (Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhi) exhibited their antibacterial potential with many of the compounds showing inhibition range of 90-100 % at 200 μg/mL, against most of the tested strains. The MIC values of some of the compounds showed good antibacterial efficacy with values ranging from 32 to 128 μg/mL. Their bacterial growth inhibitory potential was further supported by disk diffusion and growth curve assays. Interestingly, one of the Schiff's bases (LT-SB7) displayed strong synergistic activity against E. coli and S. typhi with 16-64 folds reduction in MIC values. Additionally, it exhibited up to 85 % suppression of biofilm at ^½MIC against AA209 environmental bacterial isolate and reduced the development of multidrug-resistant bacterial isolates. Promising compound LT-SB7 underwent 100 ns molecular dynamics simulations with biofilm-causing protein (PDB ID: 7C7U) to assess conformational changes and complex stability. Overall, this study identified compounds as effective antibacterial alternatives for the future.

Keywords: 4-Aminoquinoline-Isatin hybrids; Antibacterial; Antibiofilm; Antibiotic resistance; ESKAPE.