TY - JOUR
T1 - Synthesis and in vitro Study of Artemisinin/Synthetic Peroxide-Based Hybrid Compounds against SARS-CoV-2 and Cancer
AU - Herrmann, Lars
AU - Yaremenko, Ivan A.
AU - Çapcı, Aysun
AU - Struwe, Julia
AU - Tailor, Dhanir
AU - Dheeraj, Arpit
AU - Hodek, Jan
AU - Belyakova, Yulia Yu
AU - Radulov, Peter S.
AU - Weber, Jan
AU - Malhotra, Sanjay V.
AU - Terent'ev, Alexander O.
AU - Ackermann, Lutz
AU - Tsogoeva, Svetlana B.
N1 - Publisher Copyright:
© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH.
PY - 2022/5/4
Y1 - 2022/5/4
N2 - The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS-CoV-2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide-based hybrid compounds active against both cancer and SARS-CoV-2 has been reported yet. However, the hybrid drug's properties (e. g., activity and/or selectivity) can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs or bioactive natural products. In this study, a series of new artesunic acid and synthetic peroxide based new hybrids were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS-CoV-2 and leukemia cell lines. Several artesunic acid-derived hybrids exerted a similar or stronger potency against K562 leukemia cells (81–83 % inhibition values) than the reference drug doxorubicin (78 % inhibition value) and they were also more efficient than their parent compounds artesunic acid (49.2 % inhibition value) and quinoline derivative (5.5 % inhibition value). Interestingly, the same artesunic acid-quinoline hybrids also show inhibitory activity against SARS-CoV-2 in vitro (EC50 13–19 μm) and no cytotoxic effects on Vero E6 cells (CC50 up to 110 μM). These results provide a valuable basis for design of further artemisinin-derived hybrids to treat both cancer and SARS-CoV-2 infections.
AB - The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS-CoV-2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide-based hybrid compounds active against both cancer and SARS-CoV-2 has been reported yet. However, the hybrid drug's properties (e. g., activity and/or selectivity) can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs or bioactive natural products. In this study, a series of new artesunic acid and synthetic peroxide based new hybrids were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS-CoV-2 and leukemia cell lines. Several artesunic acid-derived hybrids exerted a similar or stronger potency against K562 leukemia cells (81–83 % inhibition values) than the reference drug doxorubicin (78 % inhibition value) and they were also more efficient than their parent compounds artesunic acid (49.2 % inhibition value) and quinoline derivative (5.5 % inhibition value). Interestingly, the same artesunic acid-quinoline hybrids also show inhibitory activity against SARS-CoV-2 in vitro (EC50 13–19 μm) and no cytotoxic effects on Vero E6 cells (CC50 up to 110 μM). These results provide a valuable basis for design of further artemisinin-derived hybrids to treat both cancer and SARS-CoV-2 infections.
KW - anti-SARS-CoV-2 compounds
KW - anti-cancer compounds
KW - anti-leukemia agents
KW - artemisinin based hybrids
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U2 - 10.1002/cmdc.202200005
DO - 10.1002/cmdc.202200005
M3 - Article
C2 - 35187791
AN - SCOPUS:85127237188
SN - 1860-7179
VL - 17
JO - ChemMedChem
JF - ChemMedChem
IS - 9
M1 - e202200005
ER -