Artemisinin and Quinoline Hybrid Compounds Inhibit Replication of SARS-CoV-2 In Vitro [post]

Lars Herrmann, Ivan Yaremenko, Aysun Çapcı, Julia Struwe, Jan Hodek, Yulia Belyakova, Peter Radulov, Grigoriy Stepanov, Jan Weber, Alexander Terent'ev, Lutz Ackermann, Svetlana Tsogoeva
2021 unpublished
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins (containing endoperoxide moiety) and chloroquine (containing quinoline subunit) against SARS-CoV-2 have recently been demonstrated, no study of artemisinin-and quinoline-based hybrids has been reported yet. However, the hybrid drug's
more » ... es can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs. In this study, fifteen artemisinin-and quinoline-containing hybrid compounds were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS-CoV-2 in a cytopathic effect reduction assay. All artesunic acid-containing hybrids display superior potency against SARS-CoV-2 (EC 50 values 7.8 -46 μM) and show low or no cytotoxic effects on Vero E6 cells (CC 50 up to 110 µM). The most active artesunic acid-derived hybrid is significantly more potent in vitro (EC 50 = 7.8 µM) than its parent compound artesunic acid (EC 50 >50 µM). Among quinoline-based new compounds, quinoline-adamantane (EC 50 = 1.5 μM) is the most efficient in vitro outperforming the reference drugs chloroquine (EC 50 = 3.8 µM) and remdesivir (EC 50 = 4.0 µM).
doi:10.33774/chemrxiv-2021-qlk08 fatcat:th2ee43xbjhmtden6jcbiwmofa