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Pharmacology & Therapeutics 1983
Review
Topics: Affinity Labels; Animals; Antimetabolites, Antineoplastic; Aspartate Carbamoyltransferase; Aspartic Acid; Catalysis; Cell Survival; Cells, Cultured; Computers; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Phosphonoacetic Acid; Structure-Activity Relationship; Thermodynamics
PubMed: 6361807
DOI: 10.1016/0163-7258(83)90026-8 -
Advances in Experimental Medicine and... 1993
Review
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Drug Synergism; Fluorouracil; Humans; Immunologic Factors; Phosphonoacetic Acid
PubMed: 8178714
DOI: 10.1007/978-1-4615-2488-5_17 -
Journal of Medicinal Chemistry Feb 1983Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and... (Comparative Study)
Comparative Study
Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.
Topics: Antiviral Agents; Esters; Foscarnet; Indicators and Reagents; Nucleic Acid Synthesis Inhibitors; Organophosphorus Compounds; Phosphonoacetic Acid; Simplexvirus; Structure-Activity Relationship; Viral Plaque Assay
PubMed: 6298425
DOI: 10.1021/jm00356a028 -
Langmuir : the ACS Journal of Surfaces... Mar 2018The surface modification of FeO-based magnetic nanoparticles (MNPs) with N-(phosphonomethyl)iminodiacetic acid (PMIDA) was studied, and the possibility of their use as...
The surface modification of FeO-based magnetic nanoparticles (MNPs) with N-(phosphonomethyl)iminodiacetic acid (PMIDA) was studied, and the possibility of their use as magnetic resonance imaging contrast agents was shown. The effect of the added PMIDA amount, the reaction temperature and time on the degree of immobilization of this reagent on MNPs, and the hydrodynamic characteristics of their aqueous colloidal solutions have been systematically investigated for the first time. It has been shown that the optimum condition for the modification of MNPs is the reaction at 40 °C with an equimolar amount of PMIDA for 3.5 h. The modified MNPs were characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric, and CHN elemental analyses. The dependence of the hydrodynamic characteristics of the MNP colloidal solutions on the concentration and pH of the medium was studied by the dynamic light scattering method. On the basis of the obtained data, we can assume that the PMIDA molecules are fixed on the surface of the MNPs as a monomolecular layer. The modified MNPs had good colloidal stability and high magnetic properties. The calculated relaxivities r and r were 341 and 102 mmol s, respectively. The possibility of using colloidal solutions of PMIDA-modified MNPs as a T contrast agent for liver studies in vivo (at a dose of 0.6 mg kg) was demonstrated for the first time.
Topics: Animals; CHO Cells; Cell Line, Tumor; Contrast Media; Cricetulus; Humans; Liver; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Mesocricetus; Phosphonoacetic Acid; Temperature
PubMed: 29478322
DOI: 10.1021/acs.langmuir.7b04023 -
The Journal of Biological Chemistry Jun 1987Since phosphonoformic acid (PFA) acts as a specific competitive inhibitor of Na+-Pi co-transport across renal brush-border membrane (BBM), we employed the [14C]PFA as a...
Since phosphonoformic acid (PFA) acts as a specific competitive inhibitor of Na+-Pi co-transport across renal brush-border membrane (BBM), we employed the [14C]PFA as a probe to determine the mechanism of its interaction with rat renal BBM. The binding of [14C]PFA to BBM vesicles (BBMV), with Na+ present in extravesicular medium (Na+o), was time- and temperature-dependent. The replacement of Na+o with other monovalent cations reduced the PFA binding by -80%. Cl- was the most effective accompanying monovalent anion as NaCl for maximum PFA binding. The Na+o increased the apparent affinity of BBMV for [14C]PFA binding, but it did not change the maximum binding capacity. The maximum [14C]PFA binding was achieved at Na+o approximately equal to 50 mM. The extent of Na+-dependent [14C]PFA binding correlated (r = 0.98; p less than 0.01) with percent inhibition by an equimolar dose of PFA of the (Na+o greater than Na+i)-dependent BBMV uptake of 32Pi. Intravesicular Na+ (Na+i) decreased [14C]PFA binding, on BBMV, and this inhibition by Na+i was dependent on the presence of Na+o. The increase in Na+i, at constant [Na+]o, decreased the Vmax, but not the Km, for [14C]PFA binding on BBMV. Bound [14C]PFA was displaced from BBMV by phosphonocarboxylic acids proportionally (r = 0.99; p less than 0.05) to their ability to inhibit (Na+o greater than Na+i)-gradient-dependent Pi transport, whereas other monophosphonates, diphosphonates, L-proline, or D-glucose did not influence the [14C]PFA binding. The Na+-dependent binding of [14C]PFA and of [3H]phlorizin by BBMV was 10 times higher than binding of these ligands to renal basolateral membranes and to mitochondria. [14C]PFA probably binds onto the same locus on the luminal surface of BBM, where Pi and Na+ form a ternary complex with the Na+-Pi co-transporter.
Topics: Animals; Anions; Antiviral Agents; Carbon Radioisotopes; Carrier Proteins; Cations, Monovalent; Foscarnet; Kidney Cortex; Kinetics; Male; Mannitol; Microvilli; Organophosphorus Compounds; Phosphonoacetic Acid; Protein Binding; Rats; Rats, Inbred Strains; Sodium-Phosphate Cotransporter Proteins; Symporters
PubMed: 2954950
DOI: No ID Found -
The American Journal of Physiology Feb 1987We examined the effect of phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) upon Na+-Pi cotransport in brush-border membrane (BBM) from small gut of rat. Both... (Comparative Study)
Comparative Study
We examined the effect of phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) upon Na+-Pi cotransport in brush-border membrane (BBM) from small gut of rat. Both PFA and PAA inhibited the Na+ gradient-dependent uptake of 32Pi by BBM vesicles (BBMV) prepared from intestinal mucosa but had no effect on Na+-dependent uptakes of D-[3H]glucose, L-[3H]proline, or [14C]succinate. The uptake in the absence of Na+ gradient, or uptake at equilibrium period (180 min), was not affected by PFA or by PAA. A chemical analogue of PFA and PAA, phosphonopropionic acid, had only a minor inhibitory effect and phenylphosphonic acid was inactive. Neither PFA nor PAA influenced the activity of rat intestinal BBM alkaline phosphatase. The BBMV from rat jejunum had a much higher capacity for Na+ gradient-dependent uptake of 32Pi than BBMV from duodenum or ileum. The inhibition of BBMV 32Pi transport across rat jejunum by PFA is competitive. We suggest that PFA and PAA are specific inhibitors of Na+ gradient-dependent uptake of Pi by BBMV from small intestinal mucosa and that they could serve as useful experimental tools for the studies of intestinal Na+-Pi cotransport.
Topics: Animals; Biological Transport; Carrier Proteins; Foscarnet; Intestine, Small; Kinetics; Male; Microvilli; Organophosphorus Compounds; Phosphates; Phosphonoacetic Acid; Potassium; Rats; Rats, Inbred Strains; Sodium; Sodium-Phosphate Cotransporter Proteins; Symporters
PubMed: 2950771
DOI: 10.1152/ajpgi.1987.252.2.G244 -
Journal of Medicinal Chemistry Jul 2004Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of...
Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.
Topics: Anti-HIV Agents; Cell Line; Drug Stability; Foscarnet; HIV-1; Humans; Hydrolysis; Phosphonoacetic Acid; Prodrugs; Stavudine; Stereoisomerism; Structure-Activity Relationship; Zidovudine
PubMed: 15214788
DOI: 10.1021/jm0310176 -
Journal of Acquired Immune Deficiency... 1992Induction regimens of foscarnet and ganciclovir are highly effective in arresting cytomegalovirus (CMV) retinitis in patients with AIDS. Chronic maintenance therapy is... (Review)
Review
Induction regimens of foscarnet and ganciclovir are highly effective in arresting cytomegalovirus (CMV) retinitis in patients with AIDS. Chronic maintenance therapy is nonetheless required to forestall progression of disease following induction. In open studies of these two agents in AIDS patients with CMV retinitis at dosages similar to those currently recommended, median times to retinitis progression during maintenance therapy of as long as greater than 100 days have been observed. In a randomized comparative trial of immediate and delayed foscarnet treatment utilizing rigorously defined end points, the mean times to retinitis progression were 13.3 weeks among patients receiving immediate foscarnet therapy and 3.2 weeks among those receiving no treatment. In a similar trial of ganciclovir, the mean times to progression were 68.5 days among patients receiving immediate treatment and 22.9 days among those receiving no treatment. Experience in a number of studies not designed to assess mortality has suggested that specific antiviral treatment for CMV retinitis is associated with prolongation of survival. One retrospective analysis of survival patterns in patients treated with ganciclovir has suggested a significant effect of this agent on survival; another analysis has shown no association between anti-CMV therapy and survival, with the relative hazard of death among patients receiving foscarnet therapy being equivalent to that among patients receiving ganciclovir therapy. In the one randomized study comparing the mortality of patients receiving initial treatment with either foscarnet or ganciclovir, foscarnet-treated patients had a median survival of 12.6 months compared with 8.5 months for ganciclovir-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Cytomegalovirus Infections; Drug Therapy, Combination; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Retinitis
PubMed: 1318365
DOI: No ID Found -
Cancer Chemotherapy and Pharmacology 19794'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA) and N-(phosphonacetyl)-L-aspartate (PALA) are two new anticancer agents that have been recently introduced into... (Review)
Review
4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA) and N-(phosphonacetyl)-L-aspartate (PALA) are two new anticancer agents that have been recently introduced into clinical investigation. This review summarizes the preclinical information that has accumulated with these compounds as well as the very preliminary data presently available from early clinical trials. This information indicates the promising potential of m-AMSA and PALA in the treatment of cancer.
Topics: Aminoacridines; Animals; Antineoplastic Agents; Aspartic Acid; Cell Division; Kinetics; Neoplasms, Experimental; Organophosphorus Compounds; Phosphonoacetic Acid
PubMed: 393427
DOI: 10.1007/BF00262414 -
Cancer Research Aug 1988
Review
Topics: Antineoplastic Agents; Aspartic Acid; Drug Evaluation; Drug Resistance; Humans; Organophosphorus Compounds; Phosphonoacetic Acid
PubMed: 3293772
DOI: No ID Found