Synthesis, anticancer assessment on human breast, liver and colon carcinoma cell lines and molecular modeling study using novel pyrazolo [4,3-c]pyridine derivatives

The key intermediate 3-aminopyrazolo[4,3-c]pyridine-4,6-dione (2) is considered as a precursor for some novel pyrazo lo [4,3-c] pyridines 4a-c, arylhydrazopyrazolo [4,3-c] pyrid ines 8a-e, pyrazolo [4,5,1-ij] [1,6]-naphthyridines lla-e and pyrido[4',3':3,4]pyrazolo[1,5-alpha]-pyrimidines 15a-d through Knovenegal condensation, coupling reaction and Michael addition. Some of the newly synthesized pyrazolo[4,3-c] pyridine derivatives were investigated for anticancer activity. The results of the cytotoxic activity revealed that compound 6b was the most active compound against the breast and liver carcinoma cell lines which gives IC50 values of 1.937 and 3.695 mu g/mL, respectively compared to reference drug (doxorubicin) with IC50 values of 2.527 and 4.749 mu g/ml, respectively. Moreover, compound 6c was potent compound against the colon carcinoma cell line which gives the value of IC50 = 2.914 mu g/ml compared to doxorubicin with IC50 value of 3.641 mu g/ml. Some selected of the novel synthesized compounds were docked inside the active site of ERK2 enzyme and were found display a suitable binding with the active site amino acids according to their bond lengths, angles and conformational energy. (C) 2017 Published by Elsevier Inc.