Synthesis, antitumor activity, enzyme assay, DNA binding and molecular docking ofBis-Schiff bases of pyrazoles

A novel series ofBis-Schiff bases of pyrazoles9-24were synthesized by the direct condensation of 5-aminopyrazoles4a-dwith dialdehydes8a-din ethanol. The newly synthesizedBis-Schiff bases of pyrazoles9-24were characterized and confirmed by analytical and spectroscopic data. Some selectedBis-Schiff bases were investigated for their in vitro anti-proliferation activity toward three human carcinoma cell lines {HepG2 (liver), MCF-7 (breast) and RPE-1 (normal retina pigmented epithelium)} using MTT assay. The result in vitro showed that the compound23was found to be the active candidate against HepG2 and MCF-7 cells, while compound16was found to be the most potent derivative against RPE-1 cells. All theBis-Schiff bases of pyrazoles9-24were evaluated for their screening on thymidine phosphorylase and DNA binding energy. The DNA binding energy showed that the compound12shows the lowest IC(50)compared to other series of compounds and is the nearest one to the IC(50)of the standard taxol. The molecular docking of the newBis-Schiff base9was carried out and showed good binding energies (- 4.45, - 4.95, - 2.62, - 3.83 and - 5.03 kcal/mol with 1bna, 102d, 1k2j, 2gvr and 2des double-strand DNA targets, respectively) when compared to standard doxorubicin. This study is an introduction to promising compounds.