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Titolo:
Synthesis of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-substituted-benzene thymidine mimics, some related alpha-anomers, and their evaluation as antiviral and anticancer 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: 11 - 40
SICI:
1525-7770(2001)20:1-2<11:SO1>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HERPES-SIMPLEX VIRUS; TUMOR-CELL-LINES; THYMIDYLATE SYNTHETASE; C-NUCLEOSIDES; KINASE GENE; DNA; REPLICATION; ANALOGS; DIFLUOROTOLUENE; FEASIBILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
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-benzene thymidine mimics, some related alpha-anomers, and their evaluation as antiviral and anticancer agents", NUCLEOS NUC, 20(1-2), 2001, pp. 11-40

Abstract

A group of unnatural 1-(2-deoxy-beta -D-ribofuranosyl)-2,4- difluorobenzenes having a variety of C-5 substituents (H, Me, F, CI, Br, I, CF3, CN, NO2,NH2), designed as thymidine mimics, were synthesized for evaluation as anticancer and antiviral agents. The coupling reaction of 3,5-bis-0-(p-chlorobenzoyl)-2-deoxy-alpha -D-ribofuranosyl chloride with an organocadmium reagent [(2,4-difluorophenyl)(2)Cd] afforded a mixture of the alpha- and beta -anomeric products (alpha:beta = 3:1 to 10:1 ratio). Treatment of the alpha -anomer with BF3. Et2O in nitroethane at 110-120 degreesC for 30 min was developed as an efficient method for epimerization of the major alpha -anomer to the desired beta -anomer. The 5-substituted (H, Me, CI, I, NH2) beta -anomers exhibited negligible cytotoxicity in a MTT assay (CC50 = 10(-3)-10(-4) M range), relative to thymidine (CC50 = 10(-3)-10(-5) M range), against avariety of cancer cell lines. In contrast, the 5-NO2 derivative was more cytotoxic (CC50 = 10(-5)-10(-6) M range). A number of 5-substituted beta -anomers, and some related ol-anomers, 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-3,) viruses], showed that this class of unnatural C-aryl nucleoside mimics are inactive antiviral agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 14:34:39