Synthesis and Biological Evaluation of New Piperazine Substituted 3, 5-Diarylisoxazolines

Abstract

Aim and objective: Isoxazolines are an important class of nitrogen and oxygen-containing heterocycles, which have gained much importance as the potential biological agents. In order to study structureactivity relationships of isoxazolines, this work has been conducted.

Materials and methods: A series of new piperazine substituted 3, 5-diarylisoxazoline derivatives (6-31) were designed and synthesized, and in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anticancer effect against a panel of human tumor cell lines (Hela, A549 and SGC7901) by MTT assay were evaluated.

Results: The substituents of the NH group of piperazine ring had an obvious influence on biological activities. Especially, compounds 5, 7, 8, 10, 11, 13 and 27-showed good inhibitory effect on the generation of NO compared to dexamethasone. Furthermore, derivatives 5, 6, 7, 8, 9, 13 and 26 were found to be potential selectively anticancer activity on human tumor cell lines, which displayed better cytotoxic activity to positive control 5- FU.

Conclusion: Piperazine substituted 3, 5-diarylisoxazoline derivatives could be considered as new antiinflammatory and anticancer agents.

Keywords: 3; 5-diarylisoxazoline; Piperazine; anti-inflammatory; anticancer; cytotoxicity; isoxazolines; synthesis.