In Vitro and In Silico Anti-Arboviral Activities of Dihalogenated Phenolic Derivates of L-Tyrosine

Loaiza-Cano, Vanessa; Monsalve-Escudero, Laura Milena; Restrepo, Manuel Pastrana; Quintero-Gil, Carolina; Pulido, Sergio; Galeano, Elkin; Zapata, Wildeman; Martínez-Gutiérrez, Marlen

doi:10.3390/molecules26113430

Cited by 7 publications

(5 citation statements)

References 66 publications

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“…These data are congruent with those reported for other halogenated L-tyrosines, where in vitro cytotoxicity lower than 25% was reported in the U373-MAGI cell line treated with concentrations ≤ 320 µM [14]. Similarly, our collaborators found cell viability of VERO cells up to 90% when treated with L-tyrosine-derivate compounds with free phenolic OH at a concentration of 250 µM [44]. With these results, we calculated the CC 50 for each compound, where we ruled out a cytotoxic effect as a potential mechanism to explain the viral inhibition.…”

Section: Discussionsupporting

confidence: 91%

“…This effect may be due to the action of the compound on TZM-bl cells, increasing cell proliferation, enhancing cell metabolism or gene transcription, and consequently increasing cellular and viral proteins synthesis. Our collaborators observed a similar effect in the Zika viral model, with dihalogenated compounds with chlorine and bromine structurally like ours [44]. However, further studies are needed to elucidate how viral replication is enhanced.…”

Section: Discussionsupporting

confidence: 77%

“…In contrast, the chlorinated compounds TDC-2M and TDC-3M showed antiviral activity in the R5 strain, while no antiviral activity in the X4 strain was observed (Supplementary Tables S2 and S3). These compounds were also evaluated by colleagues against other viral models; it was observed that all of them increased the production of infectious Dengue virus -2 particles but showed a potential to significantly inhibit the production of infectious viral particles of the Chikungunya virus, with inhibition percentages between 60.1% and 71.5% [44]. That suggests that the antiviral activity of these compounds depends on the viral model evaluated and that the inhibition of HIV replicative activity is not affected by exposure to brominated L-tyrosine derivates with free phenolic OH compounds, probably due to a factor inherent to the viral infection.…”

Section: Discussionmentioning

confidence: 99%

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In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1)

Serna-Arbeláez,

García-Cárcamo,

Rincón-Tabares

et al. 2023

CIMB

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HIV-1 infection is considered one of the major public health problems worldwide. Due to the limited access to antiretroviral therapy, the associated side effects, and the resistance that the virus can generate, it has become necessary to continue the development of new antiviral agents. The study aimed to identify potential antiviral agents for HIV-1 by evaluating the in vitro and in silico activity of 16 synthetic di-halogenated compounds derived from L-Tyrosine. The compounds were tested for cytotoxicity, which was determined using MTT, and a combined antiviral screening strategy (pre- and post-infection treatment) was performed against R5 and X4 strains of HIV-1. The most promising compounds were evaluated against a pseudotyped virus (HIV-GFP-VSV-G), and the effectiveness of these compounds was measured through GFP flow cytometry. Also, the antiviral effect of these compounds was evaluated in PBMCs using flow cytometry and ELISA for p24. The TODB-2M, TODC-2M, TODC-3M, and YDC-3M compounds showed low toxicity and significant inhibitory activity against HIV-1. In silico docking and molecular dynamics assays suggest that the compounds’ antiviral activity may be due to interaction with reverse transcriptase, viral protease, or envelope gp120.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1)

Serna-Arbeláez,

García-Cárcamo,

Rincón-Tabares

et al. 2023

CIMB

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“…Finally, we found that all concentrations evaluated significantly inhibited the viral protein production quantified by cell-ELISA (percentages of infection below 50%) ( Figure 1 C). 35 …”

Section: Resultsmentioning

confidence: 99%

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

et al. 2022

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Viral infections affect several million patients annually. Although hundreds of viruses are known to be pathogenic, only a few can be treated in the clinic with available antiviral drugs. Naturally based pharmacotherapy may be a proper alternative for treating viral diseases. Several natural and semisynthetic abietane-type diterpenoids have shown important antiviral activities. In this study, a biological evaluation of a number of either C-18- or C-19-functionalized known semisynthetic abietanes against Zika virus , Dengue virus , Herpes virus simplex type 1, and Chikungunya virus are reported. Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol displayed broad-spectrum antiviral properties. The scale-up synthesis of this analogue has been optimized for further studies and development. This molecule displayed an EC 50 between 5.0 and 10.0 μM against Colombian Zika virus strains and EC 50 = 9.8 μM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC 50 = 1.4 μM, DENV-2), we can conclude that this compound is a promising broad-spectrum antiviral agent paving the way for the development of novel antivirals.

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“…Previous studies have described the promotion of antiviral activity in DENV-2 when comparing a combined approach using a compound such as orlistat with individual approaches [ 46 ]. Similarly, in another flavivirus model (ZIKV/Col with derivatives of the amino acid L-tyrosine), the same result of improved inhibition via combined approaches compared with individual ones was observed [ 47 ].…”

Section: Discussionmentioning

confidence: 71%

The Antiviral and Virucidal Activities of Voacangine and Structural Analogs Extracted from Tabernaemontana cymosa Depend on the Dengue Virus Strain

Monsalve-Escudero

Loaiza-Cano

Zapata-Cardona

et al. 2021

Plants

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Currently, no specific licensed antiviral exists for treating the illness caused by dengue virus (DENV). Therefore, the search for compounds of natural origin with antiviral activity is an important area of research. In the present study, three compounds were isolated and identified from seeds of Tabernaemontana cymosa plants. The in vitro antiviral effect of those compounds and voacangine against different DENV strains was assessed using different experimental approaches: compounds added before the infection (Pre), at the same time with the virus (Trans), after the infection (Post) or compounds present in all moments of the experiment (Pre-Trans-Post, Combined treatment). In silico studies (docking and molecular dynamics) were also performed to explain the possible antiviral mechanisms. The identified compounds were three structural analogs of voacangine (voacangine-7-hydroxyindolenine, rupicoline and 3-oxo-voacangine). In the Pre-treatment, only voacangine-7-hydroxyindolenine and rupicoline inhibited the infection caused by the DENV-2/NG strain (16.4% and 29.6% infection, respectively). In the Trans-treatment approach, voacangine, voacangine-7-hydroxyindolenine and rupicoline inhibited the infection in both DENV-2/NG (11.2%, 80.4% and 75.7% infection, respectively) and DENV-2/16681 infection models (73.7%, 74.0% and 75.3% infection, respectively). The latter strain was also inhibited by 3-oxo-voacangine (82.8% infection). Moreover, voacangine (most effective virucidal agent) was also effective against one strain of DENV-1 (DENV-1/WestPac/74) and against the third strain of DENV-2 (DENV-2/S16803) (48.5% and 32.4% infection, respectively). Conversely, no inhibition was observed in the post-treatment approach. The last approach (combined) showed that voacangine, voacangine-7-hydroxyindolenine and rupicoline inhibited over 90% of infections (3.5%, 6.9% and 3.5% infection, respectively) of both strains (DENV-2/NG and DENV-2/16681). The free energy of binding obtained with an in silico approach was favorable for the E protein and compounds, which ranged between −5.1 and −6.3 kcal/mol. Finally, the complex formed between DENV-2 E protein and the best virucidal compound was stable for 50 ns. Our results show that the antiviral effect of indole alkaloids derived from T. cymose depends on the serotype and the virus strain.

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In Vitro and In Silico Anti-Arboviral Activities of Dihalogenated Phenolic Derivates of L-Tyrosine

Cited by 7 publications

References 66 publications

In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1)

In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1)

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids

The Antiviral and Virucidal Activities of Voacangine and Structural Analogs Extracted from Tabernaemontana cymosa Depend on the Dengue Virus Strain

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