Background: The continuous need for new anticancer drugs is never-ending task due to cancer resistance
to the existing drugs.
Objective: This article aimed to design, synthesis, characterization, and anticancer evaluation of cyanopyridines,
pyridopyrazolopyrimidines and pyridopyrazolotriazines.
Methods: Anticancer activity of the synthesized compounds was determined using MTT assay against three cancer
cell lines, namely liver cancer cell line (HepG-2), pancreatic cancer cell line (PANC-1), non-small lung cancer
cell line (A-549) and normal fibroblast.
Results and Discussion: A series of 3-cyanopyridines (2a,b, 4, 5, 9), pyridopyrimidine (10), pyridopyrazolopyrimidines
(11a-c, 12a,b, 18), pyrazolopyridine salt (13) and pyridopyrazolotriazines (16a,b) were synthesized
from 3-cyano-4,6-dimethyl-2-pyridone. The synthesized compounds were evaluated in vitro for their anticancer
activity and their chemical structures were determined by elemental analysis and spectroscopic data.
Conclusion: Some of the synthesized compounds showed remarkable anticancer activities, especially 11a exhibited
superior potency to the reference drug cisplatin against A-549 (IC50 = 9.24 μg mL-1 compared to 11.76 μg
mL-1 for reference drug) and was found to be safe (IC50 = 66 μg mL-1) for normal fibroblast. Furthermore, compound
16a displayed the highest activity among the tested compounds against HepG-2 (IC50 = 6.45 μg mL-1
equipotent to cisplatin) with the highest safety profile for normal fibroblast (IC50=113.97 μg mL-1).