William O. Foye

Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, United States

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Publications (106)282.03 Total impact

  • William O. Foye · Suparna Chatterji
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    ABSTRACT: The radiation-protective bis(methylthio) and methylthio amino derivatives of 1-methylpyridinium- and 1-methylquinolinium-2-dithioacetic acids, a series of non-thiol sulfur-containing compounds, have been examined for their ability to complex Cu(II) ion and remain stable in the presence of alpha-amino acids, peptides, and a protein. Copper-binding stability constants were found that were considered sufficiently large to be capable of existence under cellular conditions, with log K beta values in the range of 13-15. Copper-binding constants for alpha-amino acids are comparable to those for the radioprotective ligands, but overall binding constants for simple peptides are usually 10(4)-10(6) lower in magnitude. Essentially no change was found in the UV spectra of the Cu(II) complexes in the presence of alpha-amino acids and simple peptides, and the binding capacity to bovine serum albumin was quite low for two Cu(II) complexes of the best protective ligands, with values of 10(-6)-10(-7) M. The possibility that these radioprotectors may act in vivo as copper complexes, possibly as superoxide dismutase mimics, is thus feasible. The magnitude of the copper-binding stability constants, the lack of copper exchange between the radioprotective ligands and amino acids or peptides, and the very low tendency of the copper complexes of the radioprotective ligands to bind to a protein indicate the potential of the complexes to contribute to the radioprotective ability of the ligands.
    No preview · Article · Sep 1996 · Journal of Pharmaceutical Sciences
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    ABSTRACT: A variety of N-(alkyl/alkenyl/aryl-N-heterocyclic ureas and thioureas were synthesized as potential antihypertensives. The selected heterocyclic nuclei were the 6-substituted quinoline and the pyridine. Eleven synthesized compounds and seven related compounds in the series were evaluated orally at a dose of 100 mg/kg in conscious deoxycorticosterone acetate/saline-treated hypertensive rats by the tail-cuff method. Seventeen out of the eighteen tested compounds possessed significant antihypertensive activity (p < 0.05). 1-n-Propyl-3-[2'-(6-methoxy)quinolyl]urea (9), showing 29.1% reduction in systolic blood pressure, was the most active compound in the series. Two other compounds producing a fall in systolic blood pressure of the same magnitude were 1-allyl-3-[2'-(6-methyl)quinolyl]thiourea (4) and 1-n-propyl-3-[(2'-pyridyl)methyl]urea (17). Compound 17 with rapid onset caused significant relaxation (p < 0.01) of isolated rabbit femoral artery and guinea pig atrium but had no effect on heart rate. However, none of these exhibited higher potency than prazosin (5 mg/kg). The potency, onset, and duration of action improved when the heterocyclic nucleus was pyridine.
    No preview · Article · Apr 1996 · Journal of Pharmaceutical Sciences
  • H F Wang · X D Li · Y M Chen · L B Yuan · William O. Foye
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    ABSTRACT: High doses of 60Co radiation (4.0-8.0 Gy) in mice, rats and rabbits caused increases in rate of platelet aggregation during the first 5 days after irradiation. The inhibitory effects of the extracts of five Chinese drug plants and acetylsalicylic acid on rate of platelet aggregation were observed in both in vitro and in vivo tests, averaging 23-53% in vitro and 46-69% in vivo. Antiradiation tests on mice vs. 7.5-8.0 Gy of gamma-radiation, using the plant extracts and acetylsalicylic acid as protective agents, increased survival rates by 8-50% for the plant extracts and 35% for acetylsalicylic acid.
    No preview · Article · Oct 1991 · Journal of Ethnopharmacology
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    ABSTRACT: A series of guanylhydrazones derived from 2- and 4-pyridine and 4-quinoline carboxyaldehydes was synthesized from S-methylisothio-semicarbazide hydroiodide using known procedures. The compounds are analogous to anticancer and antiviral thiosemicarbazones, but several of the guanylhydrazones derived from 4-quinoline carboxaldehyde showed no activity against P388 lymphocytic leukemia in mice. Guanylhydrazones derived from all three heterocyclic aldehydes revealed significant blood pressure lowering effects in the rat, however.
    No preview · Article · Jun 1990 · Journal of Pharmaceutical Sciences
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    ABSTRACT: N4-(2-Acetoxyethoxymethyl)-2-acetylpyridine thiosemicarbazone (AATSC) belongs to a series of molecules known to have broad antimicrobial inhibitory activity. These molecules contain the 2-acetoxyethoxy moiety which could conceivably take up a conformation analogous to that of the ribosyl group. Moreover, the thiosemicarbazone moiety, when in the presence of a suitable enzymatic site, could mimic the triazine group, which is found in a number of antifolate drugs. AATSC, which has both bacterial inhibitory activity and water solubility, was accordingly evaluated for its antifolate activity against the bovine liver dihydrofolate reductase. AATSC is shown to be a fully uncompetitive inhibitor of that enzyme. Furthermore, AATSC enhances the activity of methotrexate. Such a potentiation could be useful for therapeutic purposes.
    No preview · Article · May 1990 · Biochimica et Biophysica Acta
  • Panna Lal Dutta · William O. Foye
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    ABSTRACT: Series of N-substituted diethyl aspartates and N-substituted-3-oxo-1,4-piperazine-2-acetic acid esters were synthesized as potential inhibitors of aspartate transcarbamoylase. The aspartates were obtained by addition of substituted alkyl amines to diethyl maleate, or conversion of the hydroxy ethyl amino adduct to other functions. The 3-oxo-1,4-piperazine-2-acetic acid esters were prepared by addition of ethylene diamine to diethyl maleate, followed by cyclization. Addition of 1,2-diamino-2-methylpropane gave the corresponding 5,5-dimethyl-3-oxo-1,4-piperazine-2-acetic acid ester. N-Acyl derivatives in each series were obtained using the bromoacyl chlorides. A majority of the compounds in each series showed antimicrobial activity against five representative microorganisms, as well as significant activity against aspartate transcarbamoylase. Four of the compounds were found to have significant specificity against several tumor cell lines. A distance of two carbons between N and a reactive function was found to give the best activity for either antimicrobial, antienzyme, or tumor cell specificity activities, in either the open chain aspartates or cyclic piperazines. Little difference in anti-enzyme activity was found between the aspartates and piperazines, but introduction of the planar phenyl substituents lowered inhibitory activity.
    No preview · Article · May 1990 · Journal of Pharmaceutical Sciences
  • William O. Foye · Robert W. Jones · Pallab K. Ghoshal
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    ABSTRACT: The title compounds were prepared in the attempt to provide methylthio and bis(methylthio) analogues of the radioprotective pyridinium- and quinolinium-2-dithioacetic acid derivatives in which the methylthio function is attached to an amino group through an aliphatic chain. The methyl 3-amino-2-phenyldithiopropenoates were obtained by the reaction of amines with 4-phenyl-3-methylthio-1,2-dithiolium iodide, and the 1,1-bis(methylthio)-3-amino-2-phenyl-1-propenes were obtained by methylation and reduction of the dithiopropenoates. The methyl dithiopropenoates with aliphatic substituents on the nitrogen gave only fair or poor radiation protection in mice, and one example of the reduced bis(methylthio) derivatives tested was inactive. The precursor 1,2-dithiole-3-thione and its methiodide, predicted to be radiation protective, were found inactive in this test.
    No preview · Article · Oct 1987 · Journal of Pharmaceutical Sciences
  • William O. Foye · Supaporn Patarapanich
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    ABSTRACT: With the assumption that the radiation-protective ability (whole body protection of mice) of the bis(methylthio) and methylthio amino derivatives of the 1-methylquinolinium-2-dithioacetic acids may be due to complexation of copper or zinc ions in vivo, the ability of these compounds to form stable metal complexes has been observed. Metal ion stability constants have been determined for three of the compounds with Al(III), Cu(II), Fe(III), and Zn(II) ions, and stabilities somewhat larger than those for simple peptides were found. Structures of the Cu(II) and Fe(III) complexes are proposed, based on elemental analyses and infrared absorption. The Cu(II) complexes are 1:1 ligand:metal structures that precipitated as double salts with CuCl2, and the Fe(III) complexes are 2:1 structures in which the ligands incorporated an additional sulfur atom.
    No preview · Article · Aug 1987 · Journal of Pharmaceutical Sciences
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    ABSTRACT: Cyclic voltammetry data were obtained for 12 salts of quinolines, one pyridine, and one open-chain imine which possess varying degrees of anticancer activity. The structural features include sidechain bis(2-methylthio)vinyl, 2-methylthio-2-aminovinyl, dithioacetic acid, 2-quinolylvinyl, 2-styrylvinyl, and guanidine sulfide functionalities. Reduction potentials ranged from -0.43 to -1.08 V. The electrochemical results are correlated with structure. A possible mechanism of anticancer action is addressed.
    No preview · Article · Jun 1987 · Journal of Pharmaceutical Sciences
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    ABSTRACT: A new class of radiation-protective compounds has been found in the bis(methylthio) and methylthio amino derivatives of 1-methylquinolinium- and 1-methylpyridinium-2-dithioacetic acids. The compounds gave good protection to mice vs. 1000-rad gamma-radiation in ip doses of 10 mg/kg or less, much lower than those required for the aminoalkyl thiols (approximately 150-600 mg/kg). The dithioacetic acid zwitterions were prepared from the base-catalyzed reaction of carbon disulfide with quinaldine and picoline methiodides, and the bis(methylthio) derivatives resulted from reaction with methyl iodide at room temperature. Replacement of one methylthio moiety took place readily on reaction of the bis(methylthio) derivatives with 1 molar equiv of an amine. The best protective activity was found with the methylthio piperidino derivative in both the quinolinium and pyridinium series.
    No preview · Article · Feb 1987 · Journal of Medicinal Chemistry
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    ABSTRACT: A series of thiosemicarbazones and thioureas having an open-chain analogue of the ribosyl group, the 2-acetoxyethoxymethyl moiety, has been synthesized. Significant growth inhibitory activity versus gram-positive and gram-negative organisms, a yeast, and a mold has been found with the 2-acetoxyethoxymethyl derivatives of N-alkyl-, aryl-, and heteroaryl-thiosemicarbazones and thioureas. The molecules may function as inhibitors of ribonucleotide reductase or in utilization of the carbamyl group in pyrimidine biosynthesis.
    No preview · Article · Jan 1987 · Journal of Pharmaceutical Sciences
  • William O. Foye · Ali R. Banijamali · Chamnan Patarapanich
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    ABSTRACT: A series of thiosemicarbazones and thioureas having an open-chain analogue of the ribosyl group, the 2-acetoxyethoxymethyl moiety, has been synthesized. Significant growth inhibitory activity versus gram-positive and gram-negative organisms, a yeast, and a mold has been found with the 2-acetoxyethoxymethyl derivatives of N-alkyl-aryl-, and heteroaryl-thiosemicarbazones and thioureas. The molecules may function as inhibitors of ribonucleotide reductase or in utilization of the carbamyl group in pyrimidine biosynthesis.
    No preview · Article · Dec 1986 · Journal of Pharmaceutical Sciences
  • Ali R. Banijamali · William O. Foye

    No preview · Article · Nov 1986 · Journal of Heterocyclic Chemistry
  • W O Foye · V Kulapaditharom
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    ABSTRACT: A method of measuring the inhibition of sulfation of mucopolysaccharides employed the coupled-enzyme system of Wortman. The procedure utilized the phenol and mucopolysaccharide sulfotransferases of rabbit liver extract. Compounds tested as inhibitors included substituted salicylic acids and related compounds, some hydroxamic acids, other agents capable of metal-ion complexation, and miscellaneous compounds, mostly containing sulfur. The most effective inhibitors were vanillin oxime, salicylhydroxamic acid, and other substituted salicylic acid derivatives of weaker acid strength than salicylic acid.
    No preview · Article · Apr 1985 · Journal of Pharmaceutical Sciences
  • William O. Foye · Vilai Kulapaditharom
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    ABSTRACT: A method of measuring the inhibition of sulfation of mucopolysaccharides employed the coupled-enzyme system of Wortman. The procedure utilized the phenol and mucopolysaccharide sulfotransferases of rabbit liver extract. Compounds tested as inhibitors included substituted salicyclic acids and related compounds, some hydroxamic acids, other agents capable of metal-ion complexation, and miscellaneous compounds, mostly containing sulfur. The most effective inhibitors were vanillin oxime, salicylhydroxamic acid, and other substituted salicylic acid derivatives of weaker acid strength than salicylic acid.
    No preview · Article · Mar 1985 · Journal of Pharmaceutical Sciences
  • William O. Foye · Ching‐Chiu Chao
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    ABSTRACT: Metal-binding stability constants for a series of N- and N,N'-substituted thioureas with Cu(II), Ni(II), Al(III), and Fe(III) ions were determined by potentiometric titration. The sequence of constants for thiourea, N-methylthiourea, and N,N'-dimethylthiourea indicated steric effects of the methyl groups and that both nitrogen and sulfur were involved in the complexation. The magnitude of the constants was somewhat lower than those of the simple peptides. The mechanism of protection against ionizing radiation by thioureas is probably due to hydrogen-atom transfer rather than binding of metal ions that catalyze cellular oxidations.
    No preview · Article · Sep 1984 · Journal of Pharmaceutical Sciences
  • William O. Foye · Seung Ho An · Timothy J. Maher
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    ABSTRACT: A simple method for obtaining the title compounds was found in the alkaline rearrangement of S-2-aminoethylisothiouronium salts, which were obtained from the condensation of thiourea or substituted thioureas with 2-bromoethylamine hydrobromide. No activity was found for the substituted guanidines against P388 lymphocytic leukemia in mice, or as H2-receptor antagonists.
    No preview · Article · Aug 1984 · Journal of Pharmaceutical Sciences
  • William O. Foye · Chaur‐Ming Jan
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    ABSTRACT: Esters of several glutathione analogues have been synthesized in which the glycine moiety was replaced by straight-chain fatty acids and the mercapto group was benzylated . Two of the derivatives (sufficiently water-soluble for the assay) were found to inhibit glyoxalase I to a greater extent than did S-methylglutathione. The two glyoxalase I inhibitors did not inhibit P388 lymphocytic leukemia in mice, however.
    No preview · Article · Apr 1984 · Journal of Pharmaceutical Sciences
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    ABSTRACT: Dihydrofolate synthetase (EC 6.3.2.12) from N. gonorrhoeae was isolated and enzyme characteristics were determined. The purified enzyme was found quite stable when stored at –60 C. About 50% of the enzyme activity wag destroyed within 6 weeks when kept at 4 C. Maximum velocity was observed at pH 9.3. The enzyme required a monovalent cation, K+ or NH4 + , and divalent cation, Mg2+ or Mn2+ for its function. ATP at 5 mM concentration gave maximum activity. Km values for dihydropteroate and L-glutamate at pH 9.3 were 3.5 10–5 M and 6.5 10–4 M, respectively. Patterns of product inhibition by dihydrofolate were found to be non-competitive with respect to dihydropteroate, having a Ki value of 5.1 0.8 10–4 M, and competitive with respect to L-glutamate, having a Ki value of 6.2 10–4 M.
    No preview · Article · Feb 1984 · Molecular and Cellular Biochemistry
  • William O. Foye · Young Ho Kim · Joel M. Kauffman
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    ABSTRACT: Reaction of 2-bis(2-methylthio)vinyl-1-methylquinolinium iodide with several heterocyclic aliphatic amines at 30-70 degrees resulted in replacement of one methylthio group to give the title compounds. Reaction with pyrrolidine gave an unidentified product lacking sulfur. Antileukemic screening against P-388 lymphocytic leukemia showed positive activity only with the 6-methyl-morpholino derivative, whereas the 6-unsubstituted morpholino derivative was inactive. This result is in contrast to previous testing results with the 2-bis(2-methylthio)vinyl compounds where both 6-substituted and 6-unsubstituted derivatives showed activity.
    No preview · Article · Nov 1983 · Journal of Pharmaceutical Sciences