Structural characterization of 5-Fluorouracil & Piperazine new solid forms and evaluation of their antitumor activity

Publication date: Available online 4 February 2020Source: Journal of Molecular StructureAuthor(s): M. Muresan-Pop, G. Chereches, G. Borodi, E. Fischer-Fodor, S. SimonAbstractA salt (FP-S) and two co-crystals (FP-C1 and FP-C2) of fluorouracil (FU) with piperazine (PZ) were investigated in terms of bioavailability and their effect on endothelial cells. From structural point of view, the best stability was observed for FP-C2 sample obtained by storage of FP-C1 sample under extreme conditions of temperature and humidity. This result was explained by the strong intermolecular interactions between 5-fluorouracil, piperazine and water, as denoted by the crystallographic analysis of FP-C2 form. Dissolution measurements in water indicate that the most soluble form is the salt, with a dissolution rate about 3 times greater than for the fluorouracil pure compound, while the solubility for co-crystals decreases compared to FU. Toxicity and antitumoral effect of the synthesized compounds were checked on three different cell lines: normal cells (HUVEC endothelial cells) and tumor cells (DLD-1 and HT29, both colorectal adenocarcinoma) and cytotoxicity by the MTT assay and cell proliferation assay. It has been found that the FP-C1 exerts a selective cytotoxic effect on HT29 cells and FP-C2 on DLD-1 cells in contrast to normal endothelial cell line resistance. For FU and FP-S salt, the effect on normal and tumoral cells is similar. The comparative study of the three fluorouracil forms shows t...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research