Dihydroartemisinin-Ursodeoxycholic Bile Acid Hybrids in the Fight against SARS-CoV-2.

Autor:	Marchesi E; Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy., Gentili V; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Bortolotti D; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Preti L; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Marchetti P; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Cristofori V; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Fantinati A; Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy., Rizzo R; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Trapella C; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy., Perrone D; Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy., Navacchia ML; Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), Via P. Gobetti 101, I-40129 Bologna, Italy.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2023 Nov 14; Vol. 8 (47), pp. 45078-45087. Date of Electronic Publication: 2023 Nov 14 (Print Publication: 2023).
DOI:	10.1021/acsomega.3c07034
Abstrakt:	Here, we propose the molecular hybridization of dihydroartemisinin (DHA) and ursodeoxycholic bile acid (UDCA), approved drugs, for the preparation of antiviral agents against SARS-CoV-2. DHA and UDCA were selected on the basis of their recently demonstrated in vitro activity against SARS-CoV-2. A selection of DHA-UDCA-based hybrids obtained by varying the nature of the linkage and the bile acid conjugation point as well as unconjugated DHA and UDCA were tested in vitro for cytotoxicity and anti-SARS-CoV-2 activity on Vero E6 and Calu-3 human lung cells. The hybrid DHA-t-UDCMe, obtained by conjugation via click chemistry on a gram scale, was identified as a potential candidate for SARS-CoV-2 infection treatment due to significant reduction of viral replication, possibly involving ACE2 downregulation, no cytotoxicity, and chemical stability. Competing Interests: The authors declare no competing financial interest. (© 2023 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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