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Pharmacology & Therapeutics 1989This article describes the antiviral properties of foscarnet (trisodium phosphonoformate) at the enzyme level as well as in cell cultures and in vivo. The mechanism of... (Review)
Review
This article describes the antiviral properties of foscarnet (trisodium phosphonoformate) at the enzyme level as well as in cell cultures and in vivo. The mechanism of action against herpesvirus DNA polymerases and reverse transcriptases is outlined. Clinical studies using topical foscarnet against mucocutaneous herpes simplex virus infections are presented. The clinical use of intravenous foscarnet against severe viral infections caused by cytomegalovirus, hepatitis B virus and human immunodeficiency virus is discussed.
Topics: Adolescent; Adult; Animals; Antiviral Agents; Child; Female; Foscarnet; Guinea Pigs; Humans; Male; Mice; Nucleotidyltransferases; Organophosphorus Compounds; Phosphodiesterase Inhibitors; Phosphonoacetic Acid; Rabbits; Virus Diseases; Viruses
PubMed: 2543994
DOI: 10.1016/0163-7258(89)90097-1 -
Pharmacology & Therapeutics 1982
Review
Topics: Animals; Antiviral Agents; Cell-Free System; Cells, Cultured; Chemical Phenomena; Chemistry; DNA-Directed RNA Polymerases; Foscarnet; Herpesviridae Infections; Humans; Kinetics; Nucleic Acid Synthesis Inhibitors; Organophosphorus Compounds; Phosphonoacetic Acid; Reverse Transcriptase Inhibitors; Structure-Activity Relationship; Virus Replication
PubMed: 6201932
DOI: 10.1016/0163-7258(82)90074-2 -
Journal of Medicinal Chemistry Feb 1989Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl...
Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters. The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride. Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester. Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2. The BUdR-PAA derivative and the BUdR-PFA derivative were highly active, especially the latter, which was more active than the parent nucleoside BUdR against the type 2 virus. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.
Topics: Antiviral Agents; Bromodeoxyuridine; Foscarnet; Organophosphorus Compounds; Phosphonoacetic Acid
PubMed: 2521518
DOI: 10.1021/jm00122a014 -
Archives of Ophthalmology (Chicago,... Feb 1992
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Cytomegalovirus Infections; Eye Infections, Viral; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Recurrence; Retinitis
PubMed: 1310586
DOI: 10.1001/archopht.1992.01080140041022 -
Journal of Dental Research Aug 2018Besides chemically interacting with hard tooth tissue, acidic functional monomers of self-etch adhesives should etch the prepared tooth surface to dissolve the smear...
Besides chemically interacting with hard tooth tissue, acidic functional monomers of self-etch adhesives should etch the prepared tooth surface to dissolve the smear layer and to provide surface micro-retention. Although the etching efficacy of functional monomers is commonly determined in terms of pH, the pH of adhesives cannot accurately be measured. Better is to measure the hydroxyapatite (HAp)-dissolving capacity, also considering that functional monomers may form monomer-Ca salts. Here, the etching efficacy of 6 functional monomers (GPDM, phenyl-P, MTEGP, 4-META, 6-MHP and 10-MDP) was investigated. Solutions containing 15 wt% monomer, 45 wt% ethanol, and 40 wt% water were prepared. Initially, we observed enamel surfaces exposed to monomer solution by scanning electron microscopy (SEM). X-ray diffraction (XRD) was employed to detect monomer-Ca salt formation. Phenyl-P exhibited a strong etching effect, while 10-MDP-treated enamel showed substance deposition, which was identified by XRD as 10-MDP-Ca salt. To confirm these SEM/XRD findings, we determined the etching efficacy of functional monomers by measuring both the concentration of Ca released from HAp using inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and the amount of monomer-Ca salt formation using P magic-angle spinning (MAS) nuclear magnetic resonance (NMR). ICP-AES revealed that the highest Ca concentration was produced by phenyl-P and the lowest Ca concentration, almost equally, by 4-META and 10-MDP. Only 10-MDP formed 10-MDP-Ca salts, indicating that 10-MDP released more Ca from HAp than was measured by ICP-AES. Part of the released Ca was consumed to form 10-MDP-Ca salts. It is concluded that the repeatedly reported higher bonding effectiveness of 10-MDP-based adhesives must not only be attributed to the more intense chemical bonding of 10-MDP but also to its higher etching potential, a combination the other functional monomers investigated lack.
Topics: Dental Cements; Dental Etching; Glycerolphosphate Dehydrogenase; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Materials Testing; Methacrylates; Microscopy, Electron, Scanning; Organophosphorus Compounds; Phosphonoacetic Acid; Spectrophotometry, Atomic; Surface Properties; X-Ray Diffraction
PubMed: 29554434
DOI: 10.1177/0022034518763606 -
Pharmacology & Therapeutics 1990Phosphonacetyl-L-aspartate (PALA) is a rationally-synthesized analog of the transition-state intermediate in the formation of carbamyl aspartate from carbamyl phosphate... (Review)
Review
Phosphonacetyl-L-aspartate (PALA) is a rationally-synthesized analog of the transition-state intermediate in the formation of carbamyl aspartate from carbamyl phosphate and aspartic acid by aspartate carbamyl transferase (ACTase). PALA is thus a potent inhibitor of the enzyme (Ki about 10(-8) M for ACTases of various origins), which in whole cells blocks the de novo synthesis of pyrimidines. In vivo, low doses of PALA inhibit whole body pyrimidine synthesis. While this action is cytotoxic in vitro, extensive human testing demonstrates that PALA alone is devoid of selective antitumor activity. Recent interest in the therapeutic action of PALA derives from the demonstration that its action potentiates the cytotoxicity of several cytotoxic drugs, notably 5-fluorouracil (5-FU). Results from clinical trials of PALA and 5-FU in combination in colorectal cancer suggest that biochemical modulation with regimens which follow the principles determined in preclinical studies may enhance the efficacy of current therapy.
Topics: Animals; Antineoplastic Agents; Aspartic Acid; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Fluorouracil; Humans; Neoplasms; Neoplasms, Experimental; Phosphonoacetic Acid; Pyrimidines
PubMed: 2084707
DOI: 10.1016/0163-7258(90)90055-7 -
Current Protocols in Nucleic Acid... Oct 2004Oligodeoxyribonucleotides with phosphonoacetate or thiophosphonoacetate internucleotide linkages can be made in high yield by solid-phase synthesis and possess many... (Review)
Review
Oligodeoxyribonucleotides with phosphonoacetate or thiophosphonoacetate internucleotide linkages can be made in high yield by solid-phase synthesis and possess many advantages. They are highly stable to nucleases, water-soluble, and anionic at neutral pH. They form stable duplexes with DNA and RNA, and stimulate RNase H degradation of complementary RNA. The preparation of the N,N-(diisopropylamino)phosphinyl acetate monomers from standard protected nucleosides is described here, followed by the synthesis of phosphonoacetate and thiophosphonoate oligodeoxyribonucleotides, as well as chimeric oligomers that have these modified linkages in combination with natural or phosphorothioate linkages. Purification and characterization of these oligomers is also presented.
Topics: Automation; DNA; Models, Biological; Oligodeoxyribonucleotides; Phosphonoacetic Acid; Sulfhydryl Compounds; Time Factors
PubMed: 18428930
DOI: 10.1002/0471142700.nc0424s18 -
The Medical Letter on Drugs and... Jan 1992
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Cytomegalovirus Infections; Eye Infections, Viral; Foscarnet; Humans; Phosphonoacetic Acid; Retinitis
PubMed: 1309469
DOI: No ID Found -
Journal of the American Academy of... Jul 1992
Review
Topics: Acquired Immunodeficiency Syndrome; Adult; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Humans; Male; Penile Diseases; Phosphonoacetic Acid; Retinitis; Skin Ulcer
PubMed: 1320061
DOI: 10.1016/s0190-9622(08)80827-4 -
Drugs Jun 1986
Review
Topics: Acquired Immunodeficiency Syndrome; Antimony; Antiviral Agents; Foscarnet; Humans; Interferon Type I; Phosphonoacetic Acid; Ribavirin; Suramin; Thymidine; Tungsten; Tungsten Compounds; Zidovudine
PubMed: 2942386
DOI: 10.2165/00003495-198631060-00001