2. Academic Validation
  3. Design, synthesis ADMET and molecular docking of new imidazo[4,5-b]pyridine-5-thione derivatives as potential tyrosyl-tRNA synthetase inhibitors

Design, synthesis ADMET and molecular docking of new imidazo[4,5-b]pyridine-5-thione derivatives as potential tyrosyl-tRNA synthetase inhibitors

  • Bioorg Chem. 2020 Sep;102:104105. doi: 10.1016/j.bioorg.2020.104105.
Ismail M M Othman 1,  Mohamed A M Gad-Elkareem 2,  El Hassane Anouar 3,  Kaïss Aouadi 4,  Adel Kadri 5,  Mejdi Snoussi 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt.
  • 2 Department of Chemistry, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt; Faculty of Science and Arts in Baljurashi, Albaha University, P.O. Box (1988), Albaha, Saudi Arabia.
  • 3 Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
  • 4 Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia; University of Monastir, Faculty of Sciences of Monastir, Avenue of the Environment, 5019 Monastir, Tunisia.
  • 5 Faculty of Science and Arts in Baljurashi, Albaha University, P.O. Box (1988), Albaha, Saudi Arabia; Faculty of Science of Sfax, Department of Chemistry, University of Sfax, B.P. 1171, 3000 Sfax, Tunisia. Electronic address: [email protected].
  • 6 Department of Biology, College of Science, Hail, P.O. 2440, University of Ha'il City 2440, Saudi Arabia; Laboratory of Genetics, Biodiversity and Valorization of Bio-resources (LR11ES41), University of Monastir, Higher Institute of Biotechnology of Monastir, Avenue Tahar Haddad, BP74, 5000 Monastir, Tunisia.
PMID: 32717689 DOI: 10.1016/j.bioorg.2020.104105
Abstract

In our effort of discovering new antimicrobial agents, a novel series of imidazo[4,5-b]pyridine-5-thione scaffolds were designed and synthesized and their chemical structures were characterized by physicochemical and spectral analysis. The synthesized compounds were assessed for their in vitro antimicrobial activities against pathogenic Microorganisms. Results revealed that out the tested compounds, 3 exhibited the potent inhibitory effect (MIC = 0.49 μg/mL) as compared to the positive control, chloramphenicol (0.98 μg/mL) which predicted also to have the best pharmacokinetic and druglikness properties as well as lower toxicity profiles. Preliminary structure-activity relationships (SARs) study has been also investigated. Moreover, to understand the binding patterns of the tested compounds in the Staphylococcus aureus tyrosyl-tRNA synthetase active site, molecular docking study using the most active compound 3 was carried out. The obtained results indicate that analog 3 can potentially bound to the target Enzyme with the highest docking score (-9.37 kcal/mol). Overall, our results showed that antimicrobial activity as well as ADMET and toxicity predictions were in consensus with the docking results.

Keywords

ADMET; Antimicrobial properties; Imidazo[4,5-b]pyridine-5-thione derivatives; Molecular docking; Staphylococcus aureus tyrosyl-tRNA synthetase.

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