Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker.
A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC50 in the 80-210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC50=15-30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines.
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Muszyńskiego 1, Poland. iwona.glowacka@umed.lodz.pl.
Iwona E
IE
Głowacka
Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Graciela.Andrei@rega.kleuven.be.
Graciela
G
Andrei
Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Dominique.Schols@rega.kleuven.be.
Dominique
D
Schols
Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Robert.Snoeck@rega.kleuven.be.
Robert
R
Snoeck
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Muszyńskiego 1, Poland. dorota.piotrowska@umed.lodz.pl.
Dorota G
DG
Piotrowska
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004267:DNA Viruses / Q000187:drug effects; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology; D014709:Vero Cells
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D063065:Organophosphonates; D014230:Triazoles; D006151:Guanosine
1,2,3-triazoles; acyclonucleotides; antiviral; azidophosphonates; cycloaddition; cytostatic