Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3-tris(methylthio)methyl group allowed a good stereo selectivity level. All the compounds of both enantiomeric series showed high IC50 values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule. (C) 2002 Elsevier Science Ltd. All rights reserved.

Mugnaini, C., Botta, M., Coletta, M., Corelli, F., Focher, F., Marini, S., et al. (2003). Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2 ',3 '-Dideoxv-3 '-[tris(methylthio)methyl]beta-pentofuranosyl nucleosides. BIOORGANIC & MEDICINAL CHEMISTRY, 11(3), 357-366 [10.1016/S0968-0896(02)00460-1].

Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2 ',3 '-Dideoxv-3 '-[tris(methylthio)methyl]beta-pentofuranosyl nucleosides

COLETTA, MASSIMILIANO;MARINI, STEFANO;
2003

Abstract

Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3-tris(methylthio)methyl group allowed a good stereo selectivity level. All the compounds of both enantiomeric series showed high IC50 values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule. (C) 2002 Elsevier Science Ltd. All rights reserved.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
1 [2',3' dideoxy 3' c tris(methylthio)methyl beta dextro erythro pentofuranosyl] 5 fluorouracil; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta dextro erythro pentofuranosyl]cytosine; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta dextro erythro pentofuranosyl]thymine; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta dextro erythro pentofuranosyl]uracil; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta levo erythro pentofuranosyl] 5 fluorouracil; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta levo erythro pentofuranosyl]cytosine; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta levo erythro pentofuranosyl]thymine; 1 [2',3' dideoxy 3' c tris(methylthio)methyl beta levo erythro pentofuranosyl]uracil; methyl group; nucleoside derivative; prodrug; unclassified drug; animal cell; antiviral activity; article; cell membrane; controlled study; cytotoxicity; drug screening; drug synthesis; enantiomer; IC 50; lipophilicity; medical research; molecule; mouse; nonhuman; phosphorylation; stereochemistry; 3T3 Cells; Animals; Antiviral Agents; Enzyme Inhibitors; Furans; Herpesvirus 1, Human; Inhibitory Concentration 50; Mice; Nucleosides; Phosphorylation; Stereoisomerism; Structure-Activity Relationship; Thymidine Kinase; Tumor Cells, Cultured; Human herpesvirus 1
Mugnaini, C., Botta, M., Coletta, M., Corelli, F., Focher, F., Marini, S., et al. (2003). Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2 ',3 '-Dideoxv-3 '-[tris(methylthio)methyl]beta-pentofuranosyl nucleosides. BIOORGANIC & MEDICINAL CHEMISTRY, 11(3), 357-366 [10.1016/S0968-0896(02)00460-1].
Mugnaini, C; Botta, M; Coletta, M; Corelli, F; Focher, F; Marini, S; Renzulli, M; Verri, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/67374
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