Specific inhibition of HIV-1 protease by boronated porphyrins

Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446.
Journal of Medicinal Chemistry (Impact Factor: 5.45). 10/1992; 35(18):3426-8. DOI: 10.1021/jm00096a020
Source: PubMed


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    • "BV Type I interferon induction Lehmann et al. (2010) Heme Anti-NS3/4A protease Zhu et al. (2010a) Heme HO-1 induction Shan et al. (2007), Zhu et al. (2008) ZnMP HO-1 induction and Bach 1 inhibition Hou et al. (2008) ZnMP Ubiquitination of NS5A Hou et al. (2010) Fe Antipolymerase Fillebeen et al. (2005) Fe Decreased HCV replication Yuasa et al. (2006), Zhu et al. (2010a) Fe HO-1 induction Hou et al. (2009) Zn Decreased viral replication Yuasa et al. (2006) HO-1 enzyme Enzyme overexpression Zhu et al. (2008) HBV Heme Anti-reverse transcriptase Lin and Hu (2008) HO-1 induction Protzer et al. (2007) HIV BV/BR Anti-HIV protease McPhee et al. (1996) Synthetic porphyrins Anti-HIV protease Decamp et al. (1992) Heme/MPs Anti-reverse transcriptase Levere et al. (1991), Staudinger et al. (1996), Argyris et al. (1999) HO-1 induction HO-1 induction Devadas and Dhawan (2006) MPs Gp120 inhibition Song et al. (1997) multiple viral target sites on different viruses indicates that these compounds would be also useful for patients with dual or even triple infections. Co-infected patients are a serious problem worldwide and invariably present with more severe medical disease, aggressive hepatitis, and a number of treatment dilemmas (den Brinker et al., 2000; Koziel and Peters, 2007; Zhou et al., 2011). "
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    ABSTRACT: Hepatitis C virus, human immunodeficiency virus, and hepatitis B virus are chronic viral infections that cause considerable morbidity and mortality throughout the world. In the decades following the identification and sequencing of these viruses, in vitro experiments demonstrated that heme oxygenase-1, its oxidative products, and related compounds of the heme oxygenase system inhibit replication of all 3 viruses. The purpose of this review is to critically evaluate and summarize the seminal studies that described and characterized this remarkable behavior. It will also discuss more recent work that discovered the antiviral mechanisms and target sites of these unique antiviral agents. In spite of the fact that these viruses are diverse pathogens with quite profound differences in structure and life cycle, it is significant that heme and related compounds show striking similarity for viral target sites across all three species. Collectively, these findings strongly indicate that we should move forward and develop heme and related tetrapyrroles into versatile antiviral agents that could be used therapeutically in patients with single or multiple viral infections.
    Full-text · Article · Oct 2012 · Frontiers in Pharmacology
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    • "A cationic phthalocyanine was reported to inhibit human rhinovirus type 5 (RV-5) infection [21]. Selected porphyrin derivatives inhibit specific viral targets including retroviral reverse transcriptase [22-26] and HIV-1 protease [27]. "
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    ABSTRACT: Prevention of poxvirus infection is a topic of great current interest. We report inhibition of vaccinia virus in cell culture by porphyrins and phthalocyanines. Most previous work on the inhibition of viruses with tetrapyrroles has involved photodynamic mechanisms. The current study, however, investigates light-independent inhibition activity. The Western Reserve (WR) and International Health Department-J (IHD-J) strains of vaccinia virus were used. Virucidal and antiviral activities as well as the cytotoxicity of test compounds were determined. Examples of active compounds include zinc protoporphyrin, copper hematoporphyrin, meso(2,6-dihydroxyphenyl)porphyrin, the sulfonated tetra-1-naphthyl and tetra-1-anthracenylporphyrins, selected sulfonated derivatives of halogenated tetraphenyl porphyrins and the copper chelate of tetrasulfonated phthalocyanine. EC50 values for the most active compounds are as low as 0.05 microg/mL (40 nM). One of the most active compounds was the neutral meso(2,6-dihydroxyphenyl)porphyrin, indicating that the compounds do not have to be negatively charged to be active. Porphyrins and phthalocyanines have been found to be potent inhibitors of infection by vaccinia virus in cell culture. These tetrapyrroles were found to be active against two different virus strains, and against both enveloped and non-enveloped forms of the virus, indicating that these compounds may be broadly effective in their ability to inhibit poxvirus infection.
    Preview · Article · Jun 2003 · BMC Infectious Diseases
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    • "They have been studied in this capacity as photoactivated insecticides (Amor et al., 2000) and for use in treating Alzheimer's disease and myasthenia gravis (Antuono, 1995; Lenigk et al., 2000). Porphyrins have been shown to inhibit telomerase and Hepatitis C virus serine protease (Wheelhouse, et al., 1998) while metalloporphyrins have been shown to be potent inhibitors of human immunodeficiency virus (HIV) type 1 and 2 reverse transcriptases (DeCamp et al., 1992). Porphyrins have also been shown to bind to DNA (Mestre et al., 1996; Mohammadi et al., 1998) and are used in photodynamic therapy (Griffiths et al., 1998). "
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    ABSTRACT: Monosulfonate tetraphenyl porphyrin (TPPS(1)) forms a 1:1 complex with electric eel acetylcholinesterase (AChE) inducing a loss in TPPS(1) absorbance at 402 nm and the appearance of a new absorbance centered at 442 nm. In the presence of AChE, the fluorescence of TPPS(1) at 652 nm is slightly narrowed, with the maximal 652 nm fluorescence shifted from 407 to 412 nm excitation wavelength. The fluorescence peak of TPPS(1) at 712 nm shifts to 716 nm in the presence of AChE. TPPS(1) is a competitive inhibitor of AChE. The addition of acetylcholine iodide (AChI) or the competitive inhibitor tetracaine to the preformed AChE-TPPS(1) complex results in a loss of the 442 nm absorbance band as the porphyrin is displaced from AChE. The absorbance peak does not decrease in the presence of procaine, a non-competitive inhibitor.
    Full-text · Article · Jul 2002 · Biosensors & Bioelectronics
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