Inhibition of HIV-1 Reverse Transcriptase and Protease by Phlorotannins from the Brown Alga Ecklonia cava

Abstract

The reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) converts the single-stranded (ϩ) viral RNA genome into a double-stranded proviral DNA prior to its integration into the host genomic DNA. The RT is a multifunctional enzyme with three recognized enzymatic activities of RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H activities. HIV-1 protease is an aspartic protease required for the proteolytic processing of the large Gag and Gag-Pol viral polyprotein precursors into the mature virion structural proteins, as well as the virion enzymes. These two enzymes, HIV-1 RT and protease, have key roles in HIV replication and inhibition of these enzymes along with HIV-1 integrase has been a major target of acquired immunodeficiency syndrome (AIDS) therapy. 1)In addition to the well-known nucleoside RT inhibitors (NRTIs), zidovudine (AZT), didanosine (ddC), zalcitabine (ddT), stavudine (d4T), lamivudine (3TC), and abacavir (ABC), non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, delavirdine, and efavirenz have been formally approved to treat HIV infection. On the other hand, saquinavir, ritonavir, and indinavir are the three main HIV protease inhibitors available today. A number of inhibitors interacting with RT have been isolated from plants (baicalin, avarol, avarone, and psychotrine) and marine resources (illimaquinone, peyssonol, and KM043). [2][3][4] In the case of HIV-1 protease, natural products, such as mangostin, ursolic, and maslinic acid, have been reported to show inhibitory activity against this enzyme. 5) We previously reported the results of screening inhibitory activities of 47 types of Korean seaweed on HIV-1 RT and found that the EtOAc fraction of Ecklonia cava strongly inhibited the RDDP activity of this enzyme. 6) In this study, we report the isolation of four phlorotannin compounds containing dibenzo [1,4]dioxin elements in common from E. cava and the kinetic study of HIV-1 RT by 8,8Ј-bieckol (2) that showed the most potent inhibitory effect on this enzyme. MATERIALS AND METHODS MaterialsThe thalli of E. cava KJELLMAN were collected from the coasts of Korea including Sungsanpo, Wando, and Namhaedo from January 1999 to June 2000. After cleaning the surface of the thalli with water to remove visible epiphytes and dirt, samples were dried at 60°C for 12 h in an oven and then ground in a coffee grinder. This seaweed was identified by Prof. S. M. Boo of the Department of Biology, Chungnam National University, Korea, and Prof. Y. S. Oh of the Department of Aquaculture, Gyeongsang National University, Korea. A voucher specimen (SSI-06) was deposited in the Herbarium of the Department of Biological Sciences, Sungkyunkwan University.Extraction and Isolation The dried thalli (1 kg) of E. cava were extracted three times with 100% MeOH and evaporated in vacuo. The MeOH extract (180 g) was dissolved in water and partitioned with n-hexane. After the H 2 O layer was further partitioned with ethyl acetate, the organic solvent fraction was c...

Anti-HIV-1 activity of phlorotannin derivative 8,4‴-dieckol from Korean brown alga Ecklonia cava

“…27) Numerous bioactivities of phlorotannins have been reported up to date such as antioxidant, anti-inflammatory, 28) antibacterial, 29) and anti-MMP activities. 30) Furthermore, Ahn et al 31) claimed that phloroglucinol derivative 8,8'-bieckol inhibited the activity of recombinant RT and protease of HIV-1 in vitro. Artan et al 32) reported the enhanced HIV-1 inhibitory effect of a phloroglucinol derivative, 6,6′-bieckol, from E. cava.…”

Penyahbauan Fukoidan dan Kesannya terhadap Ciri Fizikokimia dan Aktiviti Antipengoksidaan

“…Antaranya termasuklah antikoagulan, antitrombotik, antiviral, antitumor, imunomodulat, antikeradangan, pengurang lemak darah, antioksidan, aktiviti melawan hepatopati, uropati dan nefropati, perlindungan kesan gastrik dan potensi terapeutik dalam pembedahan (Ale 2012;Li et al 2008;Synytsya et al 2006). Permintaan yang tinggi daripada pengguna untuk makanan yang diproses secara minimum dan mengandungi bahan pengawet semula jadi, kajian secara mendalam terhadap pengekstrakan antioksidan alternatif semula jadi dan sebatian antimikrob semakin giat dijalankan (AbuGhannam & Gupta 2010;Ahn et al 2004;Andarwulan et al 2010;Apostolidis, Ayaz et al 2008;Chew et al 2008;Cox et al 2008;Rajauria et al 2010).…”

Feeding the Abalone Haliotis discus hannai with the Seaweed Eisenia bicyclis Allows the Accumulation of Phlorotannins

“…All compounds were isolated on the basis of retention times. Phlorotannin content was assessed by measuring the dimensions of HPLC peaks and comparing these with those of and Glombitza, 1986) and exhibit a variety of physiological activities, including antioxidant (Yoon et al, 2011), antidiabetic (Okada et al, 2004), antimicrobial (Eom et al, 2011), anti-inflammatory Kang et al, 2013), and antihypertensive properties; they inhibit melanogenesis (Heo et al, 2009), metalloproteinases , and reverse transcriptase (Ahn et al, 2004), induce quinine reductase (Yoon et al, 2013), and exert depressive effects on the central nervous system (Cho et al, 2012). However, E. bicyclis has a bitter tannin-rich taste; it is also tough in texture and is thus unappetizing.…”