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Titolo:
Synthesis of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-substituted-benzenes: "Thymine replacement" analogs of thymidine for evaluation as anticancer and antiviral agents
Autore:
Wang, ZX; Duan, WL; Wiebe, LI; Balzarini, J; De Clercq, E; Knaus, EE;
Indirizzi:
Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada Univ Alberta Edmonton AB Canada T6G 2N8 Sci, Edmonton, AB T6G 2N8, Canada Catholic Univ Louvain, Rega Inst Med Res, B-3000 Louvain, Belgium CatholicUniv Louvain Louvain Belgium B-3000 es, B-3000 Louvain, Belgium
Titolo Testata:
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
fascicolo: 1-2, volume: 20, anno: 2001,
pagine: 41 - 58
SICI:
1525-7770(2001)20:1-2<41:SO1>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
HERPES-SIMPLEX VIRUS; NUCLEOSIDE ANALOGS; THYMIDYLATE SYNTHETASE; KINASE GENE; ANTIHERPES ACTIVITY; REPLICATION; PYRIMIDINE; DIFLUOROTOLUENE; INHIBITION; MECHANISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Knaus, EE Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada Univ Alberta Edmonton AB Canada T6G 2N8 ton, AB T6G 2N8, Canada
Citazione:
Z.X. Wang et al., "Synthesis of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-substituted-benzenes: "Thymine replacement" analogs of thymidine for evaluation as anticancer and antiviral agents", NUCLEOS NUC, 20(1-2), 2001, pp. 41-58

Abstract

A group of unnatural 1-(2-deoxy-beta -D-ribofuranosyl)-2,4-difluorbenzeneshaving a variety of C-5 two-carbon substituents II-CC-X, X = I, Br; -Cr=CH; (E)- CH=CH-X, X = I, Br; - CH=CH2; - CH2CI1; -CH(N-3) CH2Br], designed asnucleoside mimics, were synthesized for evaluation as anticancer and antiviral agents. The 5-substituted (E)-CH=CH-I and -CH2CH3 compounds exhibited negligible cytotoxicity in a MTT assay (CC50 = 10(-3) to 10(-4)M range), relative to thymidine (CC50 10-3 to 10(-5) M range), against a variety of cancer cell lines. In contrast, the C-5 substituted -C=C-I and -CH(N-3)CH2Br compounds were more cytotoxic (CC50 = 10(-5) to 10(-6) M range). The -C=C-I and -CH2CH3 compounds exhibited similar cytotoxicity against non-transfected (KBALB, 143B) and HSV-1 TK+ gene transfected (KBALB STK, 143B-LTK) cancercell lines expressing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK+). This observation indicates that expression of the viral TKenzyme did not provide a gene therapeutic effect. The parent group of 5-substituted compounds, that were evaluated using a wide variety of antiviral assay systems [HSV-1, HSV-2, varicella-zoster virus (VZV), vaccinia virus, vesicular stomatitis, cytomegalovirus (CMV), and human immunodeficiency (HIV-1, HIV-2) viruses], showed that this class of unnatural C-aryl nucleosidemimics are inactive and/or weakly active antiviral agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/02/20 alle ore 05:24:21