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

Jenny-Lee Panayides; Véronique Mathieu; Laetitia Moreno Y Banuls; Helen Apostolellis; Nurit Dahan-Farkas; Hajierah Davids; Leonie Harmse; M E Christine Rey; Ivan R Green; Stephen C Pelly; Robert Kiss; Alexander Kornienko; Willem A L van Otterlo

doi:10.1016/j.bmc.2016.04.036

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. Epub 2016 Apr 20.

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: wvo@sun.ac.za.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects*
Humans
Neoplasms / drug therapy
Nucleosides / chemical synthesis
Nucleosides / chemistry*
Nucleosides / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Nucleosides