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Structure-aided optimization of 3-O-β-chacotriosyl ursolic acid as novel H5N1 entry inhibitors with high selective index
- Source :
- Bioorganic & Medicinal Chemistry. 27:4048-4058
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Currently, entry inhibitors contribute immensely in developing a new generation of anti-influenza virus drugs. Our earlier studies have identified that 3-O-β-chacotriosyl ursolic acid (1) could inhibit H5N1 pseudovirus by targeting hemagglutinin (HA). In the present study, a series of C-28 modified pentacyclic triterpene saponins via conjugation with a series of amide derivatives were synthesized and their antiviral activities against influenza A/Duck/Guangdong/99 virus (H5N1) in MDCK cells were evaluated. The SARs analysis of these compounds revealed that introduction of certain amide structures at the 17-COOH of ursolic acid could significantly enhance both their antiviral activity and selective index. This study indicated that the attachment of the methoxy group or Cl atom to the phenyl ring at the ortho- or para-position was crucial to improve inhibitory activity. Mechanism studies demonstrated that these title triterpenoids could bind tightly to the viral envelope HA to block the attachment of viruses to host cells, which was consistent with docking studies.
- Subjects :
- Stereochemistry
Clinical Biochemistry
Pharmaceutical Science
medicine.disease_cause
01 natural sciences
Biochemistry
Virus
Structure-Activity Relationship
chemistry.chemical_compound
Triterpenoid
Viral envelope
Ursolic acid
Triterpene
Amide
Drug Discovery
medicine
Humans
Molecular Biology
chemistry.chemical_classification
Influenza A Virus, H5N1 Subtype
010405 organic chemistry
Chemistry
Organic Chemistry
Antineoplastic Agents, Phytogenic
Triterpenes
Influenza A virus subtype H5N1
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Docking (molecular)
Molecular Medicine
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....018291cdcd4d25f9637618f6104dc3c8