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Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains
- Source :
- Molecules; Volume 16; Issue 5; Pages: 4264-4277, Molecules, Molecules, Vol 16, Iss 5, Pp 4264-4277 (2011)
- Publication Year :
- 2011
- Publisher :
- Molecular Diversity Preservation International, 2011.
-
Abstract
- The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1(Ⅲ)(B) induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC₅₀) at 16.90 μM and a therapeutic index (TI) above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic protease inhibitor resistant strains. A combination of docking and pharmacophore methods clarified possible binding modes of mangiferin in the HIV-1 protease. The pharmacophore model of mangiferin consists of two hydrogen bond donors and two hydrogen bond acceptors. Compared to pharmacophore features found in commercially available drugs, three pharmacophoric elements matched well and one novel pharmacophore element was observed. Moreover, molecular docking analysis demonstrated that the pharmacophoric elements play important roles in binding HIV-1 protease. Mangiferin is a novel nonpeptidic protease inhibitor with an original structure that represents an effective drug development strategy for combating drug resistance.
- Subjects :
- Models, Molecular
Anti-HIV Agents
medicine.medical_treatment
Xanthones
Pharmaceutical Science
Drug resistance
Biology
mangiferin
HIV-1
protease
anti-HIV agents
drug resistance
Article
Analytical Chemistry
Cell Line
lcsh:QD241-441
chemistry.chemical_compound
Therapeutic index
lcsh:Organic chemistry
HIV Protease
Catalytic Domain
Drug Discovery
Drug Resistance, Viral
medicine
Humans
Physical and Theoretical Chemistry
Mangiferin
Protease
Organic Chemistry
Drug development
Biochemistry
chemistry
Chemistry (miscellaneous)
Docking (molecular)
Cell culture
Mutation
Leukocytes, Mononuclear
Molecular Medicine
Pharmacophore
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules; Volume 16; Issue 5; Pages: 4264-4277
- Accession number :
- edsair.doi.dedup.....c4a2cfcb42e1f6b87b058495054b5282
- Full Text :
- https://doi.org/10.3390/molecules16054264