2. Academic Validation
  3. New antiglioma zwitterionic pronucleotides with an FdUMP framework

New antiglioma zwitterionic pronucleotides with an FdUMP framework

  • Eur J Med Chem. 2018 Jan 20:144:682-691. doi: 10.1016/j.ejmech.2017.12.070.
Agnieszka Szymanska-Michalak 1,  Dariusz Wawrzyniak 1,  Grzegorz Framski 1,  Jacek Stawinski 1,  Jan Barciszewski 1,  Adam Kraszewski 2
Affiliations

Affiliations

  • 1 Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.
  • 2 Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland. Electronic address: akad@ibch.poznan.pl.
PMID: 29289891 DOI: 10.1016/j.ejmech.2017.12.070
Abstract

We have designed and synthesized new 5-fluoro-2'-deoxyuridine 5'-phosphate pronucleotides which can function as potential agents against the glioblastoma multiforme tumor. Their anti-malignant potency has been tested against T98G, U-118 MG, U-87 MG gliomas, HeLa, and Caco-2 Cancer cell lines, using MRC-5 healthy cells as a reference. Five of the sixteen compounds (4c, 4f-i) exhibited significant Anticancer potency and high selectivity indices (SI 12-66). It is likely that these zwitterionic pronucleotides may function in a similar manner to zwitterionic Phospholipids, by inducing cell membrane charge disorder, making the cell permeable to bioactive agents. The most promising therapeutic pronucleotides 4c, 4f-h, have high intestinal-blood uptake potency (Caco-2 cell line), and may be considered as potential, orally administrated, Anticancer drugs.

Keywords

Anticancer; FdUMP; GBM; Glioblastoma multiforme; Nucleotide analogues; Pronucleotides; Zwitterions.

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