2. Academic Validation
  3. Green and rapid and instrumental one-pot method for the synthesis of imidazolines having potential anti-SARS-CoV-2 main protease activity

Green and rapid and instrumental one-pot method for the synthesis of imidazolines having potential anti-SARS-CoV-2 main protease activity

  • Sustain Chem Pharm. 2023 Sep:34:101136. doi: 10.1016/j.scp.2023.101136.
Sabikeh Azimi 1,  Muna S Merza 2,  Fatemeh Ghasemi 3,  Hasan Ali Dhahi 4,  Farid Baradarbarjastehbaf 5,  Mehdi Moosavi 6,  Pouya Ghamari Kargar 1,  Christophe Len 7 8
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Sciences, University of Birjand, Birjand, 97175-615, Iran.
  • 2 Prosthetic Dental Techniques Department, Al-Mustaqbal University College, Babylon, 51001, Iraq.
  • 3 MSC in Software Engineering, Kowsar, The Institute of Higher Education, Ministry of Science, Research and Technology, Computer Engineering Department, Qazvin, Iran.
  • 4 National University of Science and Technology, Dhi Qar, Iraq.
  • 5 Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, University of Pécs, Pécs, Hungary.
  • 6 Department of Chemistry, Faculty of Chemistry, Mazandaran University, Babolsar, Iran.
  • 7 Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, 11 Rue Pierre et Marie Curie, F-75005, Paris, France.
  • 8 Sorbonne Universités, Universite de Technologie de Compiegne, F- 60200, Compiegne, France.
PMID: 37333050 DOI: 10.1016/j.scp.2023.101136
Abstract

The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is responsible for ongoing epidemics in humans and some other mammals and has been declared a public health emergency of international concern. In this project, several small non-peptide molecules were synthesized to inhibit the major proteinase (Mpro) of SARS-CoV-2 using rational strategies of drug design and medicinal chemistry. Mpro is a key Enzyme of coronaviruses and plays an essential role in mediating viral replication and transcription in human lung epithelial and stem cells, making it an attractive drug target for SARS-CoV. The Antiviral potential of imidazoline derivatives as inhibitors of (SARS-CoV-2) Mpro was evaluated using in-silico techniques such as molecular docking simulation, molecular dynamics (MD), and ADMET prediction. The docking scores of these imidazoline derivatives were compared to that of the N3 crystal inhibitor and showed that most of these compounds, particularly compound E07, interacted satisfactorily in the active site of the coronavirus and strongly interacted with the residues (Met 165, Gln 166, Met 165, His 41, and Gln 189). Furthermore, the results were confirmed by MD simulations after exposure to long-term MD simulations and ADMET predictions.

Keywords

Imidazolines; In-silico studies; N-Bromosaccharin (NBSac); SARS-CoV-2) Mpro.

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