Synthesis, antimicrobial evaluation and docking study of novel 3,5-disubstituted-2-isoxazoline and 1,3,5-trisubstituted-2-pyrazoline derivatives

Ahmed H. Ismail, Ahmed M. Abdula*, Ivan H.R. Tomi, Ali H.R. Al-Daraji, Younis Baqi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Background: The frequent use of antibacterial agents leads to antimicrobial resistance, which is one of the biggest threats to global health today. Therefore, the discovery of novel antimi-crobial agents is still urgently needed to overcome the severe infections caused by these putative pathogens resistant to currently available drugs. Objective: The present work was aimed to synthesize and investigate the preliminary structure-activity relationships (SARs) of isoxazoline and pyrazoline derivatives as antimicrobial agent. Methods: Target compounds were obtained in a multistep reaction synthesis and the antimicrobial activity was investigated in several species; two-gram negative (Escherichia coli and Pseudo-monas aeruginosa), two-gram positive (Staphylococcus aureus and Bacillus subtilis) and one fungi (Candida albicans), using cup-plate agar diffusion method. The most potent compounds were docked into glucosamine-6-phosphate synthase (GlcN-6-P), the molecular target enzyme for an-timicrobial agents, using Autodock 4.2 program. Results: Herein, thirteen novel target compounds were synthesized in moderate to good isolated yield. Based on the SARs, two compounds (2c and 5c) were found to be potent antimicrobial agents on all tested targets, recording potency higher than amoxicillin, the standard antimicrobial drug. Compound 2b identified as selective for gram-negative, while compound 7a found to be selective for gram-positive. The hit compounds (2c, 5a, 5c and 5d) were subjected to a docking study on glucosamine-6-phosphate synthase (GlcN-6-P). All hits were found to bind to the orthos-teric (active) site of the enzyme, which might represent a competitive mechanism of inhibition. Conclusion: The newly synthesized heterocyclic compounds could serve as potent leads for the development of novel antimicrobial agents.

Original languageEnglish
Pages (from-to)462-473
Number of pages12
JournalMedicinal Chemistry
Issue number5
Publication statusPublished - 2021


  • Antimicrobial
  • Chalcone
  • Docking
  • Isoxazoline
  • Pyrazoline
  • Synthesis

ASJC Scopus subject areas

  • Drug Discovery

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