Nucleosides and nucleotides. 152. 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside
1996; Elsevier BV; Volume: 6; Issue: 16 Linguagem: Inglês
10.1016/0960-894x(96)00339-3
ISSN1464-3405
AutoresAkira Matsuda, Hideshi Hattori, Motohiro Tanaka, Takuma Sasaki,
Tópico(s)RNA modifications and cancer
Resumo1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)uracil (EUrd) has been designed as a potential multifunctional antitumor nucleoside antimetabolite. EUrd was synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-d-ribo-pentofuranose (6) and bis(trimethylsilyl)uracil in the presence of trimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH3/MeOH. In vitro tumor cell growth inhibitory activity of EUrd against 14 human solid tumor cell lines was compared with 5-fluorouridine (FUrd), 2′-deoxy-5-fluorouridine (FdUrd), and 5-fluorouracil (5-FU) as positive controls. EUrd was a quite potent tumor cell growth inhibitor against almost all the tumor cell lines examined in this study except for human pancreas PANC-1 cells, and the potency of EUrd is about 6 to 650 times stronger than that of 5-FU and comparable to that of FUrd and FdUrd. EUrd showed also potent antitumor activity against human tumors as xenografts in nude mice when given in a daily intravenous dose of 2 mg/kg on consecutive days.
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