Journal
MOLECULES
Volume 16, Issue 5, Pages 4264-4277Publisher
MDPI
DOI: 10.3390/molecules16054264
Keywords
mangiferin; HIV-1; protease; anti-HIV agents; drug resistance
Funding
- 973 Program [2009CB522306]
- Eleventh Five-Year Key Scientific and Technological Program of China [2009ZX09501-029, 2008ZX10001-002, 2009ZX09103-414]
- CAS [KSCX1-YW-10, KSCX2-YW-R-185]
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The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1(IIIB) induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50) at 16.90 mu M 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.
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