Chemical synthesis,molecular modelling,and evaluation of anticancer activity of some pyrazol-3-one Schiff base derivatives

A series of twelve pyrazol-3-one Schiff`s base derivatives (5–17) were designed and synthesized by microwave-assisted chemical synthesis. Their purity was confirmed by melting point and HPLC and their chemical structures were determined by FT-IR, UV, <sup>1</sup>H, and <sup>13</sup>C-NMR spectroscopic techniques. In silico docking of the synthesized compounds inside the active site of thymidine phosphorylase was performed using two molecular modeling programs. The compounds were tested in vitro on calf thymus DNA to study the interaction with DNA using a spectrophotometer. Some of the pyrazol-3-one Schiff`s base derivatives showed close match interaction with DNA. The tested compounds were also studied by application to angiogenic enzyme thymidine phosphorylase (TP, E.C. 2.4.2.4), carcinoma cell lines including both human breast (MCF-7) and human lung cell lines (A549). The lead compound 2 in the series caused inhibition of thymidine phosphorylase in the micro molar range (IC₅₀ of 28 ± 2 µM) and was able to retard growing of breast carcinoma cells. Our results indicate that pyrazol-3-one Schiff base derivatives are promising lead compounds for the development of more active antitumor agents and exhibit their highest cytotoxic effect on breast carcinoma cell line.