Synthesis, Cytotoxic Activity and Molecular Modelling of Novel [1,2,3]triazolo[4,5-d]pyrimidine Compounds, their Glycoside Derivatives and Acyclic Analogs

Abstract

Novel substituted [1,2,3]triazolo[4,5-d]pyrimidine-7-one derivatives were synthesized using 1,2,3-triazolo-4-carboxamide derivative (2) by the reaction with carbon disulfide, triethoxymethane, 4-fluorobenzaldehyde and ethyl benzoate respectively. The S-glucoside, N-glycoside derivatives and acyclic sugar analogs of new synthesized [1,2,3]triazolo[4,5-d]pyrimidines were also synthesized. The synthesized compounds were tested for cytotoxicity and in vitro anticancer activity versus human lung (A549), colon (HCT116) and breast (MCF-7) cancer cell lines. The results disclosed that the synthesized compounds apply their activities in A549 and MCF-7. MCF-7 cells are more sensitive to the tested compounds than the other cell lines. Compounds 2, 3, 9 and 10 exposed promising anticancer activities compared to the action of the ordinarily used anticancer drug, doxorubicin in both A549 and MCF-7 cell lines. A good binding affinities for compounds 2, 3, 6, 10 and 11 were noted in docking studies. Results showed a clear effect of N3-substitution in pyrimidine ring on the activities of the synthesized compounds