Synthesis and in vitro growth inhibitory activity of novel silyl- and trityl-modified nucleosides

  • Bioorg Med Chem. 2016 Jun 15;24(12):2716-24. doi: 10.1016/j.bmc.2016.04.036.
Jenny-Lee Panayides  1 ,  Véronique Mathieu  2 ,  Laetitia Moreno Y Banuls  2 ,  Helen Apostolellis  3 ,  Nurit Dahan-Farkas  3 ,  Hajierah Davids  4 ,  Leonie Harmse  3 ,  M E Christine Rey  5 ,  Ivan R Green  6 ,  Stephen C Pelly  6 ,  Robert Kiss  2 ,  Alexander Kornienko  7 ,  Willem A L van Otterlo  8
Affiliations
  • 1. Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, Johannesburg 2050, South Africa; Pioneering Health Sciences, CSIR Biosciences, PO Box 395, Pretoria 0001, South Africa.
  • 2. Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
  • 3. Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, PO Wits, Johannesburg 2050, South Africa.
  • 4. Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, PO Wits, Johannesburg 2050, South Africa; Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth 6031, South Africa.
  • 5. School of Molecular and Cellular Biology, University of the Witwatersrand, PO Wits, Johannesburg 2050, South Africa.
  • 6. Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Matieland 7602, South Africa.
  • 7. Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
  • 8. Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, Johannesburg 2050, South Africa; Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Matieland 7602, South Africa. Electronic address: [email protected].
PMID: 27157005 DOI: 10.1016/j.bmc.2016.04.036
Abstract

Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentration of 100μM against a small panel of tumor cell lines (HL-60, K-562, Jurkat, Caco-2 and HT-29). The entire set was also tested at varying concentrations against two human glioma lines (U373 and Hs683) to obtain GI50 values, with the best results being values of ∼25μM.

Keywords
1,3-Dihydroxy-1,1,3,3-tetraisopropyldisiloxane; Antiproliferative activities; Dimethoxytrityl; Nucleosides; Silyl protecting groups; tert-Butyldimethylsilyl.