Synthesis and in vitro Study of Artemisinin/Synthetic Peroxide‐Based Hybrid Compounds against SARS‐CoV‐2 and Cancer

Synthesis and in vitro Study of Artemisinin/Synthetic Peroxide‐Based Hybrid Compounds against SARS‐CoV‐2 and Cancer Full article

Journal

ChemMedChem
ISSN: 1860-7179 , E-ISSN: 1860-7187

Output data

Year: 2022, Volume: 17, Number: 9, Article number : e202200005, Pages count : DOI: 10.1002/cmdc.202200005

Authors

Lars Herrmann ¹ , Yaremenko Ivan A. ² , Aysun Çapcı ¹ , Julia Struwe ³ , Dhanir Tailor ⁴ , Arpit Dheeraj ⁴ , Jan Hodek ⁵ , Belyakova Yulia Yu. ² , Radulov Peter S. ² , Jan Weber ⁵ , Sanjay Malhotra V. ⁶ , Terent'ev Alexander O. ² , Lutz Ackermann ^7,8 , Tsogoeva Svetlana B. ⁹

Affiliations

1	Friedrich Alexander University Erlangen Nuremberg: Friedrich-Alexander-Universitat Erlangen-Nurnberg, Department of Chemistry and Pharmacy, GERMANY.
2	Zelinsky Institute of Organic Chemistry RAS: Institut organiceskoj himii imeni N D Zelinskogo RAN, -, RUSSIAN FEDERATION.
3	Georg-August-Universität Göttingen: Georg-August-Universitat Gottingen, -, GERMANY.
4	Oregon Health & Science University, Department of Cell, Developmental and Cancer Biology, UNITED STATES.
5	Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 16610 Prague, Czech Republic
6	Oregon Health & Science University, Department of Cell, Development and Cancer Biology, UNITED STATES.
7	German Center for Cardiovascular Research (DZHK) Potsdamer Str. 58 10785 Berlin Germany
8	Institut für Organische und Biomolekulare Chemie Georg-August-Universität Göttingen Tammannstraße 2 37077 Göttingen Germany
9	Institut für Organische Chemie, Friedrich-Alexander Universität Erlangen-Nürnberg, Department Chemie und Pharmazie, Henkestrasse 42, 91054, Erlangen, GERMANY.

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.

Lars H. , Yaremenko I.A. , Aysun Ç. , Julia S. , Dhanir T. , Arpit D. , Jan H. , Belyakova Y.Y. , Radulov P.S. , Jan W. , Sanjay M.V. , Terent'ev A.O. , Lutz A. , Tsogoeva S.B.
Synthesis and in vitro Study of Artemisinin/Synthetic Peroxide‐Based Hybrid Compounds against SARS‐CoV‐2 and Cancer
ChemMedChem. 2022. V.17. N9. e202200005 . DOI: 10.1002/cmdc.202200005 WOS Scopus OpenAlex

Web of science:	WOS:000774531500001
Scopus:	2-s2.0-85127237188
OpenAlex:	W4213112613

DB	Citing
OpenAlex	24
Scopus	23
Web of science	19