Next Article in Journal
Pressure-Induced Polymorphism of Caprolactam: A Neutron Diffraction Study
Previous Article in Journal
Avocado Oil: Characteristics, Properties, and Applications
Open AccessArticle

Synthesis and Cytostatic Effect of 3’-deoxy-3’-C-Sulfanylmethyl Nucleoside Derivatives with d-xylo Configuration

1
Department of Pharmaceutical Chemistry, University of Debrecen, 4032 Debrecen, Egyetem Tér 1, Hungary
2
Department of Biotechnology and Microbiology, University of Debrecen, 4032 Debrecen, Egyetem Tér 1, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Ramachandra S. Hosmane
Molecules 2019, 24(11), 2173; https://doi.org/10.3390/molecules24112173
Received: 21 May 2019 / Revised: 5 June 2019 / Accepted: 8 June 2019 / Published: 10 June 2019
A small library of 3’-deoxy-C3’-substituted xylofuranosyl-pyrimidine nucleoside analogues were prepared by photoinduced thiol-ene addition of various thiols, including normal and branched alkyl-, 2-hydroxyethyl, benzyl-, and sugar thiols, to 3’-exomethylene derivatives of 2’,5’-di-O-tert-butyldimethylsilyl-protected ribothymidine and uridine. The bioactivity of these derivatives was studied on tumorous SCC (mouse squamous carcinoma cell) and immortalized control HaCaT (human keratinocyte) cell lines. Several alkyl-substituted analogues elicited promising cytostatic activity in low micromolar concentrations with a slight selectivity toward tumor cells. Near-infrared live-cell imaging revealed SCC tumor cell-specific mitotic blockade via genotoxicity of analogue 10, bearing an n-butyl side chain. This analogue essentially affects the chromatin structure of SCC tumor cells, inducing a condensed nuclear material and micronuclei as also supported by fluorescent microscopy. The results highlight that thiol-ene chemistry represents an efficient strategy to discover novel nucleoside analogues with non-natural sugar structures as anticancer agents. View Full-Text
Keywords: xylofuranosyl nucleoside; cytostatic; genotoxic; squamous carcinoma cell line (SCC); radical thiol-ene coupling; time-lapse imaging video-microscopy xylofuranosyl nucleoside; cytostatic; genotoxic; squamous carcinoma cell line (SCC); radical thiol-ene coupling; time-lapse imaging video-microscopy
Show Figures

Graphical abstract

MDPI and ACS Style

Bege, M.; Kiss, A.; Kicsák, M.; Bereczki, I.; Baksa, V.; Király, G.; Szemán-Nagy, G.; Szigeti, M.Z.; Herczegh, P.; Borbás, A. Synthesis and Cytostatic Effect of 3’-deoxy-3’-C-Sulfanylmethyl Nucleoside Derivatives with d-xylo Configuration. Molecules 2019, 24, 2173.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop