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Synthesis and In Vitro Anti-Influenza Virus Evaluation of Novel Sialic Acid (C-5 and C-9)-Pentacyclic Triterpene Derivatives
- Source :
- Molecules, Molecules, MDPI, 2017, 22 (7), pp.1018. ⟨10.3390/molecules22071018⟩, Molecules, Vol 22, Iss 7, p 1018 (2017), Molecules; Volume 22; Issue 7; Pages: 1018, Molecules, 2017, 22 (7), pp.1018. ⟨10.3390/molecules22071018⟩, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS, 1H-NMR, and 13C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 μM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 μM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 μM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 μM, ~20–30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold.
- Subjects :
- 0301 basic medicine
pentacyclic triterpene
POLE 3
Proton Magnetic Resonance Spectroscopy
Pharmaceutical Science
Hemagglutinin Glycoproteins, Influenza Virus
medicine.disease_cause
01 natural sciences
influenza virus
Madin Darby Canine Kidney Cells
Analytical Chemistry
HeLa
chemistry.chemical_compound
structure-activity relationship (SAR)
Influenza A Virus, H1N1 Subtype
Triterpene
Drug Discovery
Influenza A virus
Cytotoxicity
chemistry.chemical_classification
biology
sialic acid
3. Good health
GOBS
Biochemistry
Chemistry (miscellaneous)
Molecular Medicine
Spectrometry, Mass, Electrospray Ionization
Hemagglutinin (influenza)
Antiviral Agents
Article
lcsh:QD241-441
03 medical and health sciences
Dogs
lcsh:Organic chemistry
Cell Line, Tumor
medicine
Animals
Humans
[CHIM]Chemical Sciences
MTT assay
Carbon-13 Magnetic Resonance Spectroscopy
Physical and Theoretical Chemistry
010405 organic chemistry
Organic Chemistry
biology.organism_classification
N-Acetylneuraminic Acid
Triterpenes
In vitro
0104 chemical sciences
Sialic acid
030104 developmental biology
chemistry
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules, Molecules, MDPI, 2017, 22 (7), pp.1018. ⟨10.3390/molecules22071018⟩, Molecules, Vol 22, Iss 7, p 1018 (2017), Molecules; Volume 22; Issue 7; Pages: 1018, Molecules, 2017, 22 (7), pp.1018. ⟨10.3390/molecules22071018⟩, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
- Accession number :
- edsair.doi.dedup.....960d7a9d8b195852f35148faa7a845de