Background: Triazoles and their fused derivatives are an important class of compounds
that exhibit interesting biological properties, such as antiasthmatic, antimicrobial, antifungal, analgesic,
antiallergic, antiinflammatory, herbicidal, plant growth regulative activity, and anti-HIV-1
activities. Moreover, anticancer activity of 1,2,4-triazole containing derivatives has been documented.
Due to the fact a convenient approach toward polycyclic frameworks containing fused
1,2,4-triazoles was described.
Objective: The objective of this article is the synthesis of new pyrazolo[4,3-e]triazolo[4,5-
b][1,2,4]triazine derivatives with potential antiproliferative activity.
Methods: Cancer cell proliferation was analysed by means of MTT assay after 96 h treatment. IC50
was calculated using computerized linear regression analysis of quantal log doseprobit functions,
according to the method of Litchfield and Wilcoxon. X-ray data were collected on the Bruker
SMART APEX II CCD diffractometer; The structure was solved by direct methods using
SHELXS-2013 and refined by full-matrix least-squares with SHELXL-2014/7. All calculations
were performed using WINGX version 2014.1 package.
Results: The series of pyrazolo[4,3-e]triazolo[4,5-b][1,2,4]triazine derivatives were synthesized.
MTT assay revealed that the compounds inhibited cancer cells growth at concentrations below 10
µM. The tested compounds showed higher antiproliferative activity than popular cytostatics cisplatin
(lung carcinoma) and 5-fluorouracil (colon adenocarcinoma). X-ray examinations showed
that final products in the crystalline phase have a linear form.
Conclusion: In the paper we have reported the synthesis and spectroscopic analysis of new condensed
tricyclic derivatives of the pyrazolo[4,3-e]triazolo[4,5-b][1,2,4]triazine. MTT analysis revealed
concentration-dependent decrease in lung A549 and colon LS180 cancer cells proliferation.
In order to explain the molecular mechanisms involved in anticancer activity of pyrazolo[4,3-
e]triazolo[4,5-b][1,2,4]triazine derivatives, our research will be continued.