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: 5.48). 10/1992; 35(18):3426-8. DOI: 10.1021/jm00096a020
Source: PubMed

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Available from: Charles S Craik, Aug 24, 2015
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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.
    Frontiers in Pharmacology 10/2012; 3:129. DOI:10.3389/fphar.2012.00129 · 3.80 Impact Factor
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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.
    Biosensors & Bioelectronics 07/2002; 17(6-7):463-9. DOI:10.1016/S0956-5663(01)00317-7 · 6.45 Impact Factor
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    ABSTRACT: Sulfonated porphyrins and phthalocyanines have been under consideration as microbicides, compounds which, when used in a topical formulation, can prevent transmission of the human immunodeficiency virus. Our studies have been directed toward the characterization of members of these classes. For the sulfonated phthalocyanines, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was helpful in determining the extent of sulfonation. We present the first report of spectroscopic characterization of a pentasulfonated phthalocyanine. Capillary electrophoresis data were sensitive to the concentration of the compounds (Chapter 1). Mass spectrometry was also very useful for establishing the extent of sulfonation in series of sulfonated porphyrins. Capillary electrophoresis was very useful in separating mixtures of these species. A study on sulfonation of a series of tetra(difluorophenyl)porphyrins showed that species with red-shifted Soret peaks were being formed. Data were consistent with an intramolecular sulfone bridge from the phenyl substituent to the porphyrin core. Sulfonation of the tetranaphthylporphyrins ring readily gave more than one sulfonic acid group per naphthyl side chain (Chapter 2). In cancer chemotherapy of solid tumors, it is desired to kill the tumor cells with minimal damage to the surrounding tissue. Brachytherapy seeds have been a considerable help in this regard for some tumors. In further developing approaches to selective tumor damage, we have evaluated a technique, Auger Electron Therapy (AET) in which one introduces a compound that is expected to bind to DNA, absorb the radiation, and then catalyze clustered DNA damage via release of a series of Auger electrons. We chose a series of metals (silver, indium, molybdenum, palladium, platinum, ruthenium, silver and zirconium) with appropriate energy levels to absorb an x-ray photon from the brachytherapy seed and used the tetracationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) as a scaffold. The amount of clustered DNA damage was quantitated by a plasmid assay. Experiments evaluated the effect of buffer, concentration of glycerol, irradiation time, and concentration of the porphyrin. No metal studied gave significant double stranded (localized) DNA damage. Significant single stranded DNA damage was observed, however, in the order zirconium >> ruthenium > palladium > platinum > silver ~ indium (Chapter 3). Text (Thesis). System requirements: PC, World Wide Web browser and PDF reader. Mode of access: World Wide Web. Title from title screen. Dabne White Dixon, committee chair; Kathryn Betty Grant, Markus W. Germann, committee members. Electronic text (252 p. : ill., charts (some col.)) : digital, PDF file. Thesis (Ph. D.)--Georgia State University, 2006. Includes bibliographical references. Description based on contents viewed June 18, 2007.
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