Glycosylated Flavonoids from <i>Psidium guineense</i> as Major Inhibitors of HIV-1 Replication <i>in vitro</i>

Ortega, Joseph T.; Estrada, Omar; Serrano, María Luisa Madueño; Contreras, Whendy; Orsini, Giovannina; Pujol, Flor H.; Rangel, Héctor R.

doi:10.1177/1934578x1701200712

Cited by 9 publications

(6 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This process could contribute to their accumulation within the cell. Consistent with this possibility, it has been shown that two glycosyl derivatives of quercetin (guajaverin and avicularin) have higher antiviral activity than quercetin [ 16 ]. Similar results were obtained in this study, with a reduction of two to fivefold of the EC50 with the addition of glycosyl moieties to myricetin.…”

Section: Discussionmentioning

confidence: 86%

“…Some flavonoids have been characterized as nonnucleoside inhibitors (NNRTIs) that bind to a site in the p66 subunit of the HIV-1 RT p66/p51 heterodimer, situated approximately 10 Å from the RT active site [ 14 , 15 ]. Ortega et al [ 16 ], found that quercetin, a glycosylated derivative of myricetin, exhibited an improved antiviral activity and suggested that the enhanced activity was due to the glycosyl moiety.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

et al. 2017

View full text Add to dashboard Cite

BackgroundPlant extracts are sources of valuable compounds with biological activity, especially for the anti-proliferative activity against pathogens or tumor cells. Myricetin is a flavonoid found in several plants that has been described as an inhibitor of Human immunodeficiency virus type 1 (HIV-1) through its action against the HIV reverse transcriptase, but myricetin derivatives have not been fully studied. The aim of this study was to evaluate the anti-HIV-1 activity of glycosylated metabolites obtained from Marcetia taxifolia and derived from myricetin: myricetin rhamnoside and myricetin 3-(6-rhamnosylgalactoside).MethodsCompounds were obtained from organic extracts by maceration of aerial parts of M. taxifolia. All biological assays were performed in the MT4 cell line. Antiviral activity was measured as inhibition of p24 and reverse transcriptase with a fluorescent assay.ResultsBoth flavonoids have antiviral activity in vitro, with an EC50 of 120 µM for myricetin 3-rhamnoside (MR) and 45 µM for myricetin 3-(6-rhamnosylgalactoside) (MRG), both significantly lower than the EC50 of myricetin (230 µM). Although both compounds inhibited the reverse transcriptase activity, with an IC50 of 10.6 µM for MR and 13.8 µM for MRG, myricetin was the most potent, with an IC50 of 7.6 µM, and an inhibition greater than 80%. Molecular docking approach showed correlation between the free energy of binding with the assays of enzyme inhibition.ConclusionsThe results suggest that glycosylated moiety might enhance the anti-HIV-1 activity of myricetin, probably by favoring the internalization of the flavonoid into the cell. The inhibition of the HIV-1 reverse transcriptase is likely responsible for the antiviral activity.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Some studies have reported that an improved anti‐HIV activity of flavonoids or their derivatives might be attributed to the glycosylated moiety in their chemical structures, probably by favoring the internalization of flavonoids into the target cells . Notably, trilobatin is a glycosylated derivative of phloretin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Trilobatin as an HIV‐1 entry inhibitor targeting the HIV‐1 Gp41 envelope

et al. 2018

View full text Add to dashboard Cite

HIV-1 transmembrane protein gp41 plays a crucial role by forming a stable six-helix bundle during HIV entry. Due to highly conserved sequence of gp41, the development of an effective and safe small-molecule compound targeting gp41 is a good choice. Currently, natural polyanionic ingredients with anti-HIV activities have aroused concern. Here, we first discovered that a glycosylated dihydrochalcone, trilobatin, exhibited broad anti-HIV-1 activity and low cytotoxicity in vitro. Site-directed mutagenesis analysis suggested that the hydrophobic residue (I564) located in gp41 pocket-forming site is pivotal for anti-HIV activity of trilobatin. Furthermore, trilobatin displayed synergistic anti-HIV activities combined with other antiretroviral agents. Trilobatin has a good potential to be developed as a small-molecule HIV-1 entry inhibitor for clinical combination therapy.

show abstract

“…HIV-1 (HTLV-IIIB/H9) and MT4 cells were obtained from the AIDS Research and Reference Reagent Program, Division of AIDS, The cells were grown in RPMI-1640 medium supplemented with 10% FBS and penicillin/streptomycin and splitted every 3 days.The cytotoxicity and antiviral activity were evaluated as previously described [17]. Briefly, cell cultures initially seeded at a density of 30,000 cell per well were evaluated with MTT cell proliferation assay (Sigma-USA) to determine the percentage of live cells.…”

Section: Methodsmentioning

confidence: 99%

Methoxyflavones from Marcetia taxifolia as HIV-1 Reverse Transcriptase Inhibitors

Ortega

Serrano

Suárez

et al. 2017

Natural Product Communications

Self Cite

View full text Add to dashboard Cite

Methoxyflavones are flavonoid widely distributed in plants and has been reported as potent antitumor agents and some of them have shown activity against HIV-1. In this work, two methoxyflavones isolated from Marcetia taxifolia were evaluated in vitro and in silico as HIV-1 inhibitors. Pentamethoxyflavone (5,3’-dihydroxy-3,6,7,8,4’-pentamethoxyflavone) (PMF) and Hexamethoxyflavone (5-Hydroxy-3,6,7,8,3’,4’-hexamethoxyflavone) (HMF) showed activity against HIV-1. The EC50 for HMF was 0.05 μM and 0.04 μM for PMF. The methoxyflavones also inhibited HIV-1 reverse transcriptase (RT), with an IC50 of 4.1 μM for HMF and 0.4 μM for PMF. PMF exhibited an IC50 lower than nevirapine (1.4 μM). These results are in agreement with the in silico prediction for the interaction of these flavonoids with RT. Furthermore, the effect of some methoxyflavones with different patterns of methoxylation was evaluated on RT activity in a virtual screening; found that the inhibitory activity was inversely proportional to the degree of methoxylation.

show abstract

Glycosylated Flavonoids from Psidium guineense as Major Inhibitors of HIV-1 Replication in vitro

Cited by 9 publications

References 17 publications

The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

Trilobatin as an HIV‐1 entry inhibitor targeting the HIV‐1 Gp41 envelope

Methoxyflavones from Marcetia taxifolia as HIV-1 Reverse Transcriptase Inhibitors

Contact Info

Product

Resources

About