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

Abstract

A novel series of Bis-Schiff bases of pyrazoles 9–24 were synthesized by the direct condensation of 5-aminopyrazoles 4a–d with dialdehydes 8a–d in ethanol. The newly synthesized Bis-Schiff bases of pyrazoles 9–24 were characterized and confirmed by analytical and spectroscopic data. Some selected Bis-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 compound 23 was found to be the active candidate against HepG2 and MCF-7 cells, while compound 16 was found to be the most potent derivative against RPE-1 cells. All the Bis-Schiff bases of pyrazoles 9–24 were evaluated for their screening on thymidine phosphorylase and DNA binding energy. The DNA binding energy showed that the compound 12 shows the lowest IC50 compared to other series of compounds and is the nearest one to the IC50 of the standard taxol. The molecular docking of the new Bis-Schiff base 9 was 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.