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 (CROSBI ID 133423)
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Podaci o odgovornosti
Gazivoda, Tatjana ; Šokčević, Mario ; Kralj, Marijeta ; Šuman, Lidija ; Pavelić, Krešimir ; De Clercq, Erik ; Andrei, Graciela ; Snoeck, Robert ; Balzarini, Jan ; Mintas, Mladen ; Raić-Malić, Silvana
engleski
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
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 uM). Pyrimidine derivatives of L-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3-37 uM) 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 uM), 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 uM, respectively, for compounds 3 and 9) at a approximately 5-fold lower concentration than that required to show cytotoxicity.
C-5 alkynylated pyrimidines ; C-6 alkylfuro[2, 3-d]pyrimidines ; L-ascorbic acid ; antiviral and cytostatic activity evaluations
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Podaci o izdanju
50 (17)
2007.
4105-4112
objavljeno
0022-2623
1520-4804
10.1021/jm070324z
Povezanost rada
Kemija, Temeljne medicinske znanosti