1.Synthesis and biological evaluation of (3'S)-3'-deoxy-3'-fluoro-3'-C-ethynylcytidine.
Clark JL1, Clark CB, Mason JC. Nucleosides Nucleotides Nucleic Acids. 2012 Apr;31(4):286-92. doi: 10.1080/15257770.2011.652753.
The novel pyrimidine nucleoside, (3'S)-3'-deoxy-3'-fluoro-3'-C-ethynylcytidine (1) was synthesized from cytidine in seven steps. The key step in the synthesis was the introduction of the tertiary fluorine at the 3'-position. Compound 1 was evaluated in vitro against several RNA viruses.
2.Cytotoxicity of new duplex drugs linking 3'-C-ethynylcytidine and 5-fluor-2'-deoxyuridine against human melanoma cells.
Schott S1, Niessner H, Sinnberg T, Venturelli S, Berger A, Ikenberg K, Villanueva J, Meier F, Garbe C, Busch C. Int J Cancer. 2012 Nov 1;131(9):2165-74. doi: 10.1002/ijc.27476. Epub 2012 Mar 15.
Melanoma is an increasingly common and potentially fatal malignancy of the skin and some mucous membranes. As no cure exists for metastatic disease, there is an urgent need for novel drugs. 2'-Deoxy-5-fluorouridylyl-(3'-5')-3'-C-ethynylcytidine [5-FdU(3'-5')ECyd] and 3'-C-ethynylcytidinylyl-(5' → 1-O)-2-O-octadecyl-sn-glycerylyl-(3-O → 5')-2'-deoxy-5-fluorouridine [ECyd-lipid-5-FdU] represent cytostatic active duplex drugs, which can be metabolized into various active antimetabolites. We evaluated the cytotoxicity of these heterodinucleoside phosphate analogs, their corresponding monomers ECyd and 5-FdU and combinations thereof on six metastatic melanoma cell lines and six ex vivo patient-derived melanoma cells in comparison to current standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. In vitro (real-time)-proliferation assays demonstrated that 5-FdU(3'-5')ECyd and ECyd-lipid-5-FdU had a high cytotoxic efficacy causing 75% melanoma cell death at concentrations in the nanomolar and micromolar range.
3.Effect of duplex drugs linking 2'-deoxy-5-fluorouridine (5-FdU) with 3'-C-ethynylcytidine (ECyd) on hepatoblastoma cell lines.
Eicher C1, Dewerth A, Ellerkamp V, Fuchs J, Schott S, Armeanu-Ebinger S. Pediatr Surg Int. 2013 Feb;29(2):121-7. doi: 10.1007/s00383-012-3192-5.
PURPOSE: Duplex drugs are promising anticancer agents. After in vivo cleavage into active nucleoside analogues, they exert their anti-tumour activity with reduced toxicity and side effects. Here we evaluated the impact of two duplex drugs on the viability of hepatoblastoma (HB) cells lines and their toxicity against human fibroblasts.
4.3'-ethynylcytidine, an RNA polymerase inhibitor, combined with cisplatin exhibits a potent synergistic growth-inhibitory effect via Vaults dysfunction.
Fukushima H, Abe T, Sakamoto K, Tsujimoto H, Mizuarai S, Oie S1. BMC Cancer. 2014 Aug 4;14:562. doi: 10.1186/1471-2407-14-562.
BACKGROUND: We previously reported that 3'-ethynylcytidine (ECyd, TAS-106), an RNA polymerases inhibitor, enhances the anti-tumor efficacy of platinum in several tumor types in both in vitro and in vivo tumor models. However, the molecular mechanisms underlying the ECyd-induced enhancement remain elusive.