European Journal of Medicinal Chemistry p. 1011 - 1019 (2000)
Update date:2022-08-02
Topics:
Gaubert, Gilles
Mathe, Christophe
Imbach, Jean-Louis
Eriksson, Staffan
Vincenzetti, Silvia
Salvatori, Daniela
Vita, Alberto
Maury, Georges
Although 2'-deoxy-β-D-5-azacytidine (Decitabine) and β-D-5-azacytidine display potent antileukemic properties, their therapeutic use is hampered by their sensitivity to nucleophiles and to deamination catalysed by cytidine deaminase. As shown earlier [Shafiee M., Griffon J.-F., Gosselin G., Cambi A., Vincenzetti S., Vita A., Erikson S., Imbach J.-L., Maury G., Biochem. Pharmacol. 56 (1998) 1237-1242], β-L-enantiomers of cytidine derivatives are resistant to cytidine deaminase. We thus synthesized several 5-azacytosine β-L-nucleoside analogues to evaluate their enzymatic and biological properties. 2'-Deoxy-β-L-5-azacytidine (L-Decitabine), β-L-5-azacytidine, 1-(β-L-xylo-furanosyl)5-azacytosine, and 1-(2-deoxy-β-L-threo-pentofuranosyl)5-azacytosine were stereospecifically prepared starting from L-ribose and L-xylose. D- and L-enantiomers of 2'-deoxy-β-5-azacytidine were weak substrates of human recombinant deoxycytidine kinase (dCK) compared to β-D-deoxycytidine, whereas both enantiomers of β-5-azacytidine or the L-xylo-analogues were not substrates of the enzyme. As expected, none of the presently reported derivatives of β-L-5-azacytidine was a substrate of human recombinant cytidine deaminase (CDA). The prepared compounds were tested for their activity against HIV and HBV and they did not show any significant activity or cytotoxicity. In the case of L-Decitabine, this suggests that the enantioselectivities of concerned enzymes other than dCK and CDA might not be favourable. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
View MoreContact:86-574-26865651
Address:529 YuanBaoShan Road, Beilun District
Contact:+86-0512-69209969
Address:Room 317,Lushan Road,Suzhou New District,Jiangsu Province,China.
Jiangsu Fengshan Group Co., Ltd.
Contact:86-25-86558671
Address:1903,Central International Mansion 105-6 North Zhongshan Road, Nanjing, China
JIANGSU GRAND XINYI PHARMACEUTICAL CO.,LTD
website:http://www.xypharm.com/
Contact:+86-515-84383317
Address:Chenli Road,Costal Chemical Area Binhai,Yancheng, Jiangsu,China
Shanghai He Yang International Trading Co., Ltd.
Contact:+86-21-52043598
Address:Room 816, Blag.5, No.58 Huachi Road
Doi:10.1002/1521-3773(20001201)39:23<4308::AID-ANIE4308>3.0.CO;2-4
(2000)Doi:10.1016/S0040-4020(01)00893-6
(2001)Doi:10.5560/ZNB.2014-4001
(2014)Doi:10.1021/ja00787a041
(1973)Doi:10.1016/j.molstruc.2020.128461
(2020)Doi:10.1016/0040-4020(65)80030-8
(1965)