Preparation of Tryptanthrin Derivates Bearing a Thiosemicarbazone Moiety to Inhibit SARS-CoV-2 Replication
Kateřina Veselá,
Zora Mělková,
Nikita Abramenko,
Zdeněk Kejík,
Robert Kaplánek,
Petr Dytrych,
Alla Sinica,
Oleksandra Vozniuk,
Pavel Martásek,
Milan Jakubek
Affiliations
Kateřina Veselá
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
Zora Mělková
BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Průmyslová 595, 252 50 Vestec, Czech Republic
Nikita Abramenko
BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Průmyslová 595, 252 50 Vestec, Czech Republic
Zdeněk Kejík
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
Robert Kaplánek
BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Průmyslová 595, 252 50 Vestec, Czech Republic
Petr Dytrych
Department of Surgery-Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, U Nemocnice 2, 121 08 Prague, Czech Republic
Alla Sinica
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
Oleksandra Vozniuk
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
Pavel Martásek
Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
Milan Jakubek
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
SARS-CoV-2 is a serious viral pathogen, and agents that inhibit its replication are in high demand. In the present work, we prepared two novel tryptanthrin derivates bearing a thiosemicarbazone moiety as potential antiviral agents. Both compounds displayed potent chelation activity against Fe(III/II) ion-associated COVID-19. The molecular docking results suggest that the compounds can display significant affinity towards SARS-CoV-2 papain-like proteases and SARS-CoV-2 main proteases. In addition, administering T8H-TSC can repress viral replication in the used model (Vero cells). Moreover, the therapeutic potential of the prepared compounds was predicted and analysed in terms of Lipinski’s rules, drug-likeness and drug score.
