Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 205, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2020.112664
Keywords
Pentacyclic triterpene; Rhodamine B; Fluorescent probe; Influenza virus; Subcellular localization
Categories
Funding
- National Natural Science Foundation of China [21877007, 81530090, 91753202, 21702007]
- National Key Research and Development Program of China [2016YFA0501500]
- Ministry of Science and Technology of the People's Republic of China [2019ZX09739001]
- State Key Laboratory of Phytochemistry and Plant Resources in West China
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The antiviral activity of pentacyclic triterpenes has attracted increasing attention. However, the detailed antiviral mechanism remains fully unclear. In the present study, four C28 or C30 modified pentacyclic triterpene probes via conjugating with rhodamine B were designed and synthesized, and their antiinfluenza virus activity was evaluated. The results indicated that two compounds 14 and 23 showed significant antiviral activity to influenza A/WSN/33 (H1N1) virus in Madin-Darby canine kidney (MDCK) cells with IC50 values of 8.36 and 8.24 mu M, respectively. The mechanism of action studies of representative probe 23 indicated that it could inhibit the membrane fusion by binding with influenza virus hemagglutinin (HA), and the apparent dissociation constant (K-D) value for probe 23-HA interaction was successfully evaluated (1.78 x 10(-5) M) using surface plasmon resonance spectroscopy. In addition, the subcellular localization of probe 23 in MDCK cells was determined by confocal microscopy and flow cytometry, and the results suggested that fluorescent probe 23 was rapidly taken up in MDCK cells and accumulated in cytoplasm, but no antiviral activity was observed after its entry into cells. The present study further confirmed our previous finding that pentacyclic triterpenes could tightly bind to the viral envelope HA protein, thus blocking the virus entry into host cells. (C) 2020 Elsevier Masson SAS. All rights reserved.
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