Bromotyrosine derivatives from marine sponges inhibit the HIV-1 replication in vitro
DOI:
https://doi.org/10.17533/udea.vitae.16797Keywords:
HIV-1, marine resoruces, antiviral activity, bromotyrosine, marine spongeAbstract
Background: Human immunodeficiency virus type 1 (HIV-1) infection and Acquired immunodeficiency syndrome are mayor global public health issues. HIV-1 infection is now manageable as a chronic disease thanks to the development of antiretroviral therapy; however, the existence of HIV drug resistance and collateral effects have increased the search for therapeutic alternatives. Compounds of marine resources have been studied for their antiviral potential. Objectives: To evaluate the antiviral activity of isolated bromotyrosine-derivative compounds from the Colombian marine sponges, Verongula rigida and Aiolochoria crassa against HIV-1 infection in vitro. Methods: Cytotoxicity of 11 bromotyrosine-derivative compounds was determined by the MTT assay. Inhibition of HIV-1 replication was performed using the U373-MAGI cell line, which was infected with recombinant green fluorescent protein (GFP)-expressing viruses pseudotyped, in the presence or absence of the compounds. The percentage of infected cells was evaluated by flow cytometry. In addition, the inhibition of reverse transcription and nuclear import was determined by quantification of early and late reverse transcription products and 2-LTR circles, respectively, using quantitative PCR. Results: Aeroplysinin-1, purealidin B and 3-bromo-5-hydroxy-Omethyltyrosine inhibited the HIV-1 replication in a dose-dependent manner, with a median maximum percentage of inhibition of 74% (20 μM), 57% (80 μM) and 47% (80 μM), respectively. Importantly, none of these concentrations were cytotoxic. Aeroplysinin-1, 19-deoxyfistularin 3, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-O-methyltyrosine inhibited the nuclear import efficiently; while 3,5-dibromo-N,N,N,O-tetramethyltyraminium, aeroplysinin-1, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-Omethyltyrosine inhibited X4 HIV-1 cell entry with a median maximum percentage of inhibition ranging between 2 to 30%. Conclusions: Aeroplysinin-1, 19-deoxyfistularin 3, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-O-methyltyrosine inhibited HIV replication at different steps. This study opens the possibility of chemically synthesizing these compounds and evaluating them as alternative therapies against HIV-1.
Downloads
References
Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS report on the global AIDS epidemic 2012. Geneva, Switzerland: WHO Library Cataloguing-in-Publication Data; 2012 Nov 20. 110 p.
Lehrman G, Hogue I, Palmer S, Jennings C, Spina C, Wiegand A, et al. Depletion of latent HIV-1 infection in vivo: a proof-ofconcept study. The Lancet. 2005; 366 (9485): 549-555.
Stekler J, Maenza J, Stevens C, Holte S, Malhotra U, McElrath MJ, et al. Abacavir hypersensitivity reaction in primary HIV infection. Aids. 2006; 20: 1269-1274.
Sundaram M, Saghayam S, Priya B, Venkatesh KK, Balakrishnan P, Shankar EM, et al. Changes in antioxidant profile among HIV-infected individuals on generic highly active antiretroviral therapy in southern India. Int J Infect Dis. 2008; 12: 61-66.
Kolber MA, Saenz MO, Tanner TJ, Arheart KL, Pahwa S, Liu H. Intensification of a suppressive HAART regimen increases CD4 counts and decreases CD8+ T-cell activation. Clin Immunol. 2008; 126: 315-321.
Ford PW, Gustafson KR, McKee TC, Shigematsu N, Maurizi LK, Pannell LK, et al. Papuamides A-D, HIV-inhibitory and cytotoxic depsipeptides form the sponges Theonella mirabilis and Theonella swinhoei collected in Papua New Guinea. J Am Chem Soc. 1999; 121: 5899-5909.
Qureshi A, Faulkner DJ. Haplosamates A and B: new steroidal sulfamate esters from two haploclerid sponges. Tetrahedron. 1999; 55: 8323-8330.
Rudi A, Yosief T, Loya S, Hizi A, Schleyer M, Kashman Y. Clathsterol, a novel anti-HIV-1 RT sulfated sterol from the
sponge Clathria species. J Nat Prod. 2001; 64: 1451-1453.
O’Keefe BR, Erim T, Beutler JA, Cardellina II JH, Gulakowski RJ, Krepps BL, et al. Isolation and characterization of adociavirin, a novel HIV-inhibitory protein from the sponge Adocia sp. FEBS Letters. 1998 Jul 10; 431 (1): 85-90.
Arts EJ, Hazuda DJ. HIV-1 Antiretroviral Drug Therapy. Cold Spring Harb Perspect Med. 2012; 2 (4): a007161.
Ana SE, Marisa N, Madalena H, Joao G. Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity. Mar Drugs. 2011; 9(1): 139-153.
Downloads
Published
How to Cite
Issue
Section
License
Copyright Notice and Open Access Statement
The Journal Vitae works under the Open Access license, and the published manuscripts remain available for the public, both on the Journal's website and in databases, under the Creative Commons license, "Noncommercial Attribution" and "Share alike" systems, adopted in Colombia. Hence, when the authors agree to publish in the Journal Vitae, they will not have the right to economic retributions on publications and reproductions through different diffusion media. The documents are freely available to the internet public, permitting users to read, download, copy, distribute, print, search, or link to the full texts and pass them as data to software. The only constraint on reproduction and distribution, should be to give authors control over the integrity of their work and the right to be appropriately acknowledged and cited.
Authors declare that:
-
They are the intellectual property owners and are responsible for all the information stated in the article.
-
This manuscript has not been submitted or published in other printed or digital media. They accept the responsibility for the judgments, opinions, and points of view expressed in the published article and, therefore, they exonerate Universidad de Antioquia and Journal Vitae from any process.
-
They exempt Universidad de Antioquia and Journal Vitae from settling conflicts or disputes related to the authorship of the referred article.
-
They accept the revision of the original manuscript by suitable personnel, and they bind themselves to perform the corrections appointed or suggested by the assessors.
-
Therefore, they know the editorial process and will not bind the Editorial Board of the Journal to assume any obligations regarding the volume and issue in which the article is published.
-
They transfer the rights of publication, reprinting, and distribution of the article from the moment of its approval, in print and digital format, without the right to economic rewards, and under the licensing conditions considered relevant by Journal Vitae.
-
They fully authorize Universidad de Antioquia and Journal Vitae to submit the published material to the diverse databases and indexing systems where the Journal can be found to comply with the requirements of the regulatory authorities to maintain the national classification of journals.
-
They will assume the article publication costs established for the current issue, and they will make the payment as soon as they are informed about the volume and the issue in which the final version of the article is published.
-
After the article is published, you can share digital or printed copies in a noncommercial manner. You will be able to use the paper in your institution or company for educational or research purposes, including the use in course programs.
Conflict of interest: Authors are responsible for recognizing and disclosing any financial or other benefits that could be perceived to bias their work, acknowledging all financial support and any personal connections with potential sponsors. Examples of such conflicts include receiving research funds or honoraria, serving on advisory boards, stock ownership, or employment and consulting arrangements. Authors without such connections should clearly state that they have no financial support or personal relationships that could be perceived to bias their work. All conflicts of interest should be disclosed on the author's identification page of the manuscript.
