Synthesis, biological evaluation and molecular modeling of a novel series of fused 1, 2, 3-triazoles as potential anti-coronavirus agents. Issue 21 (15th November 2018)

• Record Type: Journal Article
• Authors: Karypidou, Konstantina; Ribone, Sergio R.; Quevedo, Mario A.; Persoons, Leentje; Pannecouque, Christophe; Helsen, Christine; Claessens, Frank; Dehaen, Wim
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 21(2018)
• Page Start: 3472
• Page End: 3476
• Publication Date: 2018-11-15
• Subjects: Respiratory syndrome -- Coronavirus -- 3CL protease -- 1, 2, 3-triazole -- Biological evaluation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.09.019
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: A novel series of fused 1, 2, 3-triazoles was accessed via an organocatalytic route. Compounds14d, 14n, 14q, 18f and18i are active against coronavirus 229E. Molecular modelling work flow was developed to identify key molecular interactions. All active compounds established the key interactions based on molecular modelling. Abstract: Synthesis and biological evaluation of a novel library of fused 1, 2, 3-triazole derivatives are described. The in-house developed multicomponent reaction based on commercially available starting materials was applied and broad biological screening against various viruses was performed, showing promising antiviral properties for compounds14d, 14n, 14q, 18f and18i against human coronavirus 229E. Further in silico studies identified the key molecular interactions between those compounds and the 3-chymotrypsin-like protease, which is essential to the intracellular replication of the virus, supporting the hypothesis that the protease is the target molecule of the potential antiviral derivatives.