Exploring the purine core of 3'-C-ethynyladenosine (EAdo) in search of novel nucleoside therapeutics

  • Bioorg Med Chem Lett. 2016 Apr 15;26(8):1970-2. doi: 10.1016/j.bmcl.2016.03.005.
Fabian Hulpia  1 ,  Jan Balzarini  2 ,  Dominique Schols  2 ,  Graciela Andrei  2 ,  Robert Snoeck  2 ,  Serge Van Calenbergh  3
Affiliations
  • 1. Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
  • 2. KU Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
  • 3. Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: [email protected].
PMID: 26965865 DOI: 10.1016/j.bmcl.2016.03.005
Abstract

A series of new nucleoside analogues based on a C-3 branched ethynyl sugar derivative as present in 3'-C-ethynylcytidine (ECyd) and -adenosine (EAdo), combined with modified purine Bases was synthetized and evaluated against a broad array of viruses and tumour cell lines. The pronounced cytostatic activity of EAdo was confirmed. EAdo and its 2,6-diaminopurine analogue showed inhibitory activity against vaccinia virus (EC50: 0.31 and 51 μM, respectively). Derivative 10 on the Other hand was found active against varicella zoster virus (EC50: 4.68 μM).

Keywords
3′-C-Ethynyladenosine; Nucleosides; Vorbrüggen coupling.