Title: Synthesis and antiviral and cytostatic evaluations of the new C-5 substituted pyrimidine and furo[2,3-d]pyrimidine 4',5'-didehydro-L-ascorbic acid derivatives
Authors: Gazivoda, Tatjana ×
Sokcević, Mario
Kralj, Marijeta
Suman, Lidija
Pavelić, Kresimir
De Clercq, Erik
Andrei, Graciela
Snoeck, Robert
Balzarini, Jan
Mintas, Mladen
Raić-Malić, Silvana #
Issue Date: 13-Aug-2007
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:50 issue:17 pages:4105-4112
Abstract: The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d]pyrimidine derivatives (12-22) of l-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'-didehydro-5',6'-dideoxy-l-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of l-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 microM). Pyrimidine derivatives of l-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3-37 microM) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[2,3-d]pyrimidine derivative (12) and 6-p-bromophenylfuro[2,3-d]pyrimidine derivative (19) showed the highest cytostatic activity (IC50 = 4.5-20 microM), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 microM, respectively, for compounds 3 and 9) at a approximately 5-fold lower concentration than that required to show cytotoxicity.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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