Synthesis, Biological Evaluation and Molecular Modeling of a novel series of 1,2,3-triazoles as potential anti-coronavirus agents

KARYPIDOU, KONSTANTINA; RIBONE, S.R.; QUEVEDO, M.A.; PANNECOUQUE, CHRISTOPHE; DEHAEN, W.

Madrid

Congreso; V Symposium of Medicinal Chemistry Young Researchers; 2018

Coronaviruses are single-stranded RNA viruses associated with mild to severe respiratory syndrome (SARS-CoV).[1] To date there are no approved antiviral drugs used for the prevention and treatment of SARS-like coronaviruses making the development of an effective antiviral agent an imperative need.[2] The 3-chymotrypsin-like protease (3CLpro), also referred to as Main protease (Mpro) is essential to the viral replication inside the host cell, making it an attractive target for further development of novel inhibitors.[3] Potential antiviral agents are classified in peptidic and small molecule-based inhibitors. Reports on non-peptidic inhibitors highlight the presence of triazole motif as it forms key interactions with the catalytic dyad of the 3CLpro active site.[4] Considering our interest in the chemistry of 1,2,3-triazole bioactive molecules and their interesting binding mode, we generated a novel library of fused 1,2,3-triazoles based on a metal-free multicomponent reaction developed within our group starting from using readily available enolizable carbonyl compounds, primary amines and 4-nitrophenyl azide [Figure 1].[5] Further, the synthesized derivatives were analyzed for their antiviral properties and studies based on molecular docking were performed to identify key intermolecular interactions with the 3CLpro.