Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker

Molecules

Iwona E. Głowacka²  Graciela Andrei¹  Dominique Schols¹  Robert Snoeck¹  Dorota G. Piotrowska² 

[1] Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium; E-Mails:;Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Muszyńskiego 1, Poland; E-Mail:

关键词: azidophosphonates;    acyclonucleotides;    1;    2;    3-triazoles;    cycloaddition;    antiviral;    cytostatic;   

DOI  :  10.3390/molecules201018789

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.