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1.
Schweiz Arch Tierheilkd ; 149(7): 314-8, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17702491

ABSTRACT

This paper reports three clinical cases of needle tract implantation of neoplastic cells on the abdominal and thoracic wall after ultrasound (US) fine needle aspiration biopsy (FNAB). Primary tumors were two transitional cell carcinomas of the urinary bladder (2 dogs) and one pulmonary adenocarcinoma (1 cat). All three masses grew up along the needle tract. To our knowledge, the seeding of pulmonary adenocarcinoma cells after FNAB on the thoracic wall has never been reported in veterinary medicine.


Subject(s)
Adenocarcinoma/veterinary , Carcinoma, Transitional Cell/veterinary , Cat Diseases/pathology , Dog Diseases/pathology , Lung Neoplasms/veterinary , Neoplasm Seeding , Urinary Bladder Neoplasms/veterinary , Abdominal Wall/pathology , Adenocarcinoma/pathology , Animals , Biopsy, Fine-Needle/adverse effects , Biopsy, Fine-Needle/veterinary , Carcinoma, Transitional Cell/pathology , Cats , Diagnosis, Differential , Dogs , Fatal Outcome , Female , Lung Neoplasms/pathology , Male , Urinary Bladder Neoplasms/pathology
3.
Biochim Biophys Acta ; 1164(3): 283-8, 1993 Aug 07.
Article in English | MEDLINE | ID: mdl-8343527

ABSTRACT

A series of 3-(alkylthio)-N-hydroxysuccinimide derivatives was synthesized and their inhibitory activity towards human leukocyte elastase (HLE) was investigated. The interaction of the compounds having a 3-alkylthioether side chain (compounds 1 and 2) with HLE was found to involve rapid acylation of the enzyme, followed by total regain of enzymatic activity within 3 h. Interestingly, compounds 3-8, having an oxidized thioether side chain, were found to be highly effective, time-dependent, irreversible inhibitors of the enzyme. The k(obs)/I values for compounds 3-8 ranged between 890 and 24,000 M-1 s-1. These findings demonstrate that, unlike the physiological inhibitor of HLE (alpha-1-proteinase inhibitor), which is inactivated upon oxidation, low-molecular-weight compounds retain and/or show enhanced inhibitory activity towards HLE upon oxidation of the thioether side chain and lay the groundwork for the development of compounds that embody proteinase inhibitory and antioxidant activity.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Leukocytes/enzymology , Pancreatic Elastase/antagonists & inhibitors , Succinimides/chemical synthesis , Sulfides/chemical synthesis , Acylation , Humans , Models, Molecular , Structure-Activity Relationship , Succinimides/chemistry , Succinimides/pharmacology , Sulfides/chemistry , Sulfides/pharmacology , alpha 1-Antitrypsin/pharmacology
4.
Arch Biochem Biophys ; 297(1): 144-6, 1992 Aug 15.
Article in English | MEDLINE | ID: mdl-1637176

ABSTRACT

(RS)-Diethyl-2-benzyl-succinate was resolved using alpha-chymotrypsin. The two enantiomers were then elaborated to yield (S)-(+) and (R)-(-)-3-benzyl-N-[(methyl-sulfonyl)oxy]succinimide and the inhibitory activity of the two enantiomers toward human leukocyte elastase was subsequently determined. The k2/KI values for the R and S isomers were found to be 330 and 1500 M-1 s-1, respectively.


Subject(s)
Pancreatic Elastase/antagonists & inhibitors , Succinimides/pharmacology , Chymotrypsin , Humans , Kinetics , Leukocyte Elastase , Stereoisomerism , Succinimides/chemistry
5.
Arch Biochem Biophys ; 294(1): 144-6, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1497704

ABSTRACT

The interaction of a series of sulfonate and phosphate esters derived from N-hydroxysuccinimide with human leukocyte cathepsin G was investigated. The synthesized compounds were found to be time-dependent inhibitors of the enzyme. The composite interplay of steric and electronic effects leads to the formation of acyl enzymes of variable stability, ultimately resulting in partial or full recovery of enzymatic activity. Compounds acting via phosphorylation of the active site serine inactivated the enzyme rapidly and irreversibly.


Subject(s)
Cathepsins/antagonists & inhibitors , Neutrophils/enzymology , Phosphates/pharmacology , Sulfonic Acids/pharmacology , Acylation , Binding Sites , Cathepsin G , Humans , Kinetics , Molecular Structure , Phosphates/chemistry , Phosphoserine/metabolism , Serine Endopeptidases , Structure-Activity Relationship , Succinimides/chemistry , Sulfonic Acids/chemistry
6.
Biochemistry ; 30(17): 4132-6, 1991 Apr 30.
Article in English | MEDLINE | ID: mdl-2021604

ABSTRACT

A series of phosphate esters derived from N-hydroxysuccinimide and 3-alkyl-N-hydroxysuccinimide have been synthesized and found to be potent time-dependent irreversible inhibitors of human leukocyte elastase (HLE). The observed inhibitory activity in this series of compounds correlated well with the known preference of HLE for substrates with small hydrophobic side chains. Maximum potency was reached when a favorable aromatic interaction involving a phenyl group present in the inhibitor and an aromatic residue located in the vicinity of the S2' subsite was operative. 31P NMR spectroscopy was used to probe the mechanism of action of these compounds. Direct evidence is presented in support of a mechanism involving phosphorylation of the active site serine. These compounds constitute a new class of hydrolytically stable phosphorylating agents.


Subject(s)
Pancreatic Elastase/antagonists & inhibitors , Succinimides/pharmacology , Binding Sites , Chymotrypsin/antagonists & inhibitors , Esters/chemistry , Esters/pharmacology , Humans , Kinetics , Leukocyte Elastase , Magnetic Resonance Spectroscopy , Pancreatic Elastase/metabolism , Phosphates/chemistry , Phosphates/pharmacology , Phosphorylation , Serine Proteinase Inhibitors , Substrate Specificity , Succinimides/chemistry
7.
J Pharm Sci ; 79(10): 886-8, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2280356

ABSTRACT

A series of pyridinium and phenyl carboxylate derivatives of 3-alkyl-N-hydroxysuccinimide has been synthesized; the compounds have been shown to be highly effective, time-dependent inactivators of human leukocyte elastase. The cationic inhibitor having an isobutyl side chain as the P1 residue (3) was found to be the most effective. Human leukocyte cathepsin G and chymotrypsin are also inactivated by these compounds.


Subject(s)
Benzoates/pharmacology , Leukocytes/enzymology , Pancreatic Elastase/antagonists & inhibitors , Pyridinium Compounds/pharmacology , Succinimides/pharmacology , Benzoates/chemical synthesis , Cathepsin G , Cathepsins/antagonists & inhibitors , Chemical Phenomena , Chemistry, Physical , Chymotrypsin/antagonists & inhibitors , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Pyridinium Compounds/chemical synthesis , Serine Endopeptidases , Succinimides/chemical synthesis
9.
J Enzyme Inhib ; 3(3): 237-43, 1990.
Article in English | MEDLINE | ID: mdl-2079641

ABSTRACT

Derivatives of hydantoin have been found to inactivate human leukocyte elastase irreversibly. Chymotrypsin and cathepsin G are also inhibited by these compounds.


Subject(s)
Hydantoins/chemical synthesis , Leukocytes/enzymology , Oligopeptides/pharmacology , Pancreatic Elastase/blood , Protease Inhibitors/chemical synthesis , Amino Acid Sequence , Humans , Hydantoins/pharmacology , Indicators and Reagents , Kinetics , Molecular Sequence Data , Pancreatic Elastase/antagonists & inhibitors
10.
J Med Chem ; 32(7): 1607-11, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2738894

ABSTRACT

A series of compounds derived from 3-alkyl-N-hydroxysuccinimide have been synthesized and their inhibitory activity toward human leukocyte elastase has been investigated. Compounds having an isobutyl or isopropyl group at the C-3 position have been found to be particularly effective inactivators of the enzyme. The introduction of a trans-styryl group (as in compounds 16 and 18) results in a drastic enhancement in inhibitory activity indicative of a favorable interaction between the phenyl ring and the S2' subsite of the enzyme. The compounds were found to be highly stable in buffer solution with no apparent change in structural integrity after 17 h (the period of observation). Studies with model compounds and high-field NMR indicate that these compounds function as mechanism-based inhibitors of the enzyme. Porcine pancreatic elastase is not inhibited by these compounds, while chymotrypsin and human leukocyte cathepsin G are also efficiently inactivated.


Subject(s)
Pancreatic Elastase/antagonists & inhibitors , Succinimides/pharmacology , Animals , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , Humans , Kinetics , Leukocyte Elastase , Pancreas/enzymology , Pancreatic Elastase/metabolism , Structure-Activity Relationship , Succinimides/analysis , Swine
11.
J Med Chem ; 28(8): 1106-9, 1985 Aug.
Article in English | MEDLINE | ID: mdl-3848491

ABSTRACT

Several congeners of elasnin (I) have been synthesized and shown to inhibit human leukocyte elastase (HLE). The C-3 alkyl substituted 2-pyrones 11 and 12 were found to be the most effective inhibitors of the enzyme. These compounds are highly specific in their inhibitory activity.


Subject(s)
Lung Diseases, Obstructive/drug therapy , Pancreatic Elastase/antagonists & inhibitors , Pyridones/pharmacology , Elastin/pharmacology , Humans , In Vitro Techniques , Leukocytes/enzymology , Pyridones/chemical synthesis , Structure-Activity Relationship
12.
Biochem Biophys Res Commun ; 128(1): 90-3, 1985 Apr 16.
Article in English | MEDLINE | ID: mdl-3885950

ABSTRACT

A series of amino acid-derived sulfonate salts have been synthesized. They were found to inactivate efficiently and selectively human leukocyte elastase. The sulfonate salts of the methyl esters of L-norleucine, L-norvaline and L-valine were the most potent. The enzyme is inactivated irreversibly with concomitant release of bisulfite ion. The results demonstrate for the first time that ionic compounds can indeed function as novel inhibitors for the serine proteinases.


Subject(s)
Amino Acids/pharmacology , Protease Inhibitors , Humans , Leukocytes/enzymology , Pancreatic Elastase/antagonists & inhibitors , Serine Endopeptidases , Sulfonic Acids/pharmacology , Time Factors
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