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Titolo:
Protease inhibitors: Synthesis of L-alanine hydroxamate sulfonylated derivatives as inhibitors of Clostridium histolyticum collagenase
Autore:
Supuran, CT; Briganti, F; Mincione, G; Scozzafava, A;
Indirizzi:
Univ Florence, Lab Chim Inorgan & Bioinorgan, I-50121 Florence, Italy UnivFlorence Florence Italy I-50121 Bioinorgan, I-50121 Florence, Italy
Titolo Testata:
JOURNAL OF ENZYME INHIBITION
fascicolo: 2, volume: 15, anno: 2000,
pagine: 111 - 128
SICI:
8755-5093(2000)15:2<111:PISOLH>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN NEUTROPHIL COLLAGENASE; MATRIX METALLOPROTEINASE INHIBITORS; CARBONIC-ANHYDRASE INHIBITORS; POTENT INHIBITORS; INDIVIDUAL COLLAGENASES; CONVERTING ENZYME; THIOL INHIBITORS; DRUG DESIGN; ISOZYME-I; ACIDS;
Keywords:
collagenase; Clostridium histolyticum; L-alanine hydroxamate; zinc metalloproteinase; sulfonamide;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Supuran, CT Univ Florence, Lab Chim Inorgan & Bioinorgan, Via Gino Capponi7, I-50121 Florence, Italy Univ Florence Via Gino Capponi 7 Florence Italy I-50121 Italy
Citazione:
C.T. Supuran et al., "Protease inhibitors: Synthesis of L-alanine hydroxamate sulfonylated derivatives as inhibitors of Clostridium histolyticum collagenase", J ENZ INHIB, 15(2), 2000, pp. 111-128

Abstract

L-alanine hydroxamate derivatives were obtained by reaction of alkyl/arylsulfonyl halides with L-alanine, followed by treatment with benzyl chloride,and conversion of the COOH moiety to the CONHOH group with hydroxylamine in the presence of carbodiimides. Other derivatives were obtained by reaction of N-benzyl-alanine with aryl isocyanates, arylsulfonyl isocyanates or benzoyl isothiocyanate, followed by a similar conversion of the COOH to the CONHOH moiety. The obtained compounds were assayed as inhibitors of Clostridium histolyticum collagenase, ChC (EC 3.4.34.3), a zinc enzyme which degrades triple helical collagen. The hydroxamate derivatives were generally 100-500 times more active than the corresponding carboxylates. In the series ofsynthesized derivatives, substitution patterns leading to the most potent ChC inhibitors were those involving perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties, such as pentafluorophenylsulfonyl, 3- and 4-protected-aminophenylsulfonyl-, 3- and 4-carboxy-phenylsulfonyl-, 3-trifluoromethyl-phenylsulfonyl-, or 1- and 2-naphthylsulfonyl among others. Similarly to the matrix metalloproteinase (MMP) hydroxamate inhibitors, ChC inhibitors of the type reported here must incorporate hydrophobic moieties at the P-2' and P-3' sites, in order to achieve tight binding to the enzyme.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 08:47:48