engleski

Synthesis and cytostatic activity evaluation of pyrimidine ad purine derivatives of L-ascorbic acid

Nucleoside analogues represent a valuble source that contributes significantly to the arsenal of chemotherapeutic agents against viruses and cancer. The principal aim of this study was to synthesize the new nucleoside congeners in which the sugar ring was substituted with L-ascorbic acid moiety and to evaluate their cytostatic activity potency. L-ascorbic acid itself has been found to be cytotoxic to some human tumor cells, neuroblastoma1, osteosarcoma and retinoblastoma.2 Ascorbic acid and ascorbyl esters have been found to inhibit the proliferation of mouse glioma and human brain tumor cells, glioma (U-373) and glioblastoma (T98G) cells and renal carcinoma cells.3, 4 In addition to that we have demonstrated that pyrimidine and purine derivatives of L-ascorbic acid exert cytostatic activity against malignant cell lines, especially leukemia (IC50 = 0.9 M) and murine mammary carcinoma (IC50 = 1.4 M), as well as other malignant tumor cell lines.5 Based on this finding we have synthesized a series of pyrimidine (1-12) and purine (13-15) derivatives of L-ascorbic acid containing the free hydroxy group (7-9) at C-5 of ethylenic spacer or amino group at C-4 position (5, 6, 10-15) of the lactone ring and evaluated their cytostatic potential.

pyrimidine bases; L-ascorbic acid; cytostatic activity evaluation

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