Synthesis and In Vivo Evaluation of Pyrazolopyridine and Pyridopyrazolopyrimidine Derivatives as Potent Anticancer Agents Against Ehrlich Ascites Carcinoma

A series of pyrazolopyridines and pyridopyrazolopyrimidines have been synthesized and tested in vivo for their anticancer activity against Ehrlich ascites carcinoma. The potency of pyrazolopyridines and pyridopyrazolopyrimidines as anticancer agents was determined by evaluating their inhibition of cell growth, tumor weight loss, and mean survival time of Ehrlich ascites carcinoma-bearing mice. Most of the scaffolds synthesized showed remarkable anticancer activity; especially 4-chloro-pyridopyrazolopyrimidine (4) and N-benzylidene-pyridopyrazolopyrimidin-4-yl-hydrazine (6a) showed potent in vivo anticancer activity with percent inhibition of tumor growth of 47.62% and 47.86%, respectively. Compounds pyridopyrazolopyrimidin-4-ol (3), pyridopyrazolopyrimidin-4-yl-hydrazine (6c), methyl-pyridopyrazolopyrimidin-4-yl amine (9a), and pyrazolopyridine (11) showed excellent inhibition of tumor growth between 44 and 45%. The effect of compounds (4) and (6a) on RBCs, WBCs, and hemoglobin of the tumor-bearing mice was examined. XRD, TEM, and SEM were performed for the most active anticancer agents and showed that their size is on the nanoscale.