New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2

Israa A Seliem; Siva S Panda; Adel S Girgis; Yassmin Moatasim; Ahmed Kandeil; Ahmed Mostafa; Mohamed A Ali; Eman S Nossier; Fatma Rasslan; Aladdin M Srour; Rajeev Sakhuja; Tarek S Ibrahim; Zakaria K M Abdel-Samii; Amany M M Al-Mahmoudy

doi:10.1016/j.bioorg.2021.105117

New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2

Bioorg Chem. 2021 Sep:114:105117. doi: 10.1016/j.bioorg.2021.105117. Epub 2021 Jun 23.

Authors

Affiliations

¹ Department of Chemistry and Physics, Augusta University, Augusta, GA 30912, USA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
² Department of Chemistry and Physics, Augusta University, Augusta, GA 30912, USA. Electronic address: sipanda@augusta.edu.
³ Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
⁴ Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt.
⁵ Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
⁶ Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), Al Azhar University, Cairo, Egypt.
⁷ Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
⁸ Department of Chemistry, Birla Institute of Technology and Science, Pilani, India.
⁹ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
¹⁰ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.

Abstract

At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-e) by incorporating 1,2,3-triazole were synthesized via a modified microwave-assisted click chemistry technique. Among the synthesized conjugates, 4-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-fluoro-2-(trifluoromethyl)quinoline (10g) and 6-fluoro-4-(2-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)ethoxy)-2-(trifluoromethyl)quinoline (12c) show high potency against SARS-CoV-2. The selectivity index (SI) of compounds 10g and 12c also indicates the significant efficacy compared to the reference drugs.

Keywords: Click chemistry; Molecular docking; Quinoline; SARS-CoV-2; Triazole.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
COVID-19 Drug Treatment*
Click Chemistry
Humans
Molecular Docking Simulation
Quinolines / chemical synthesis*
Quinolines / chemistry
SARS-CoV-2
Triazoles / chemical synthesis*
Triazoles / chemistry

Substances

Antiviral Agents
Quinolines
Triazoles