Bis(2-furanylmethyl)monospiro(N/N)cyclotriphosphazenes: synthesis, structural characterization, antiproliferative, and antimigratory activity studies

Abstract In this study, the condensation reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (HCCP) with N 1,N3 -bis(furan-2-ylmethyl)-1,3-diamino-propane (1) yielded tetrachlorobis(2-furanyl-methyl)monospiro(N/N)cyclotriphosphazene (2). Fully substituted tetraaminobis(2-furanylmethyl)-spiro(N/N)cyclotriphosphazenes (2a and 2b) were obtained by Cl replacement reactions with excess pyrrolidine and piperidine, respectively, using dry THF under reflux of 2. The structures of the phosphazenes were confirmed by data obtained by elemental analysis, FT-IR, ESI-MS, 1H, 13C, and 31P NMR. Moreover, the molecular structure of 2b was elucidated by X-ray crystallography. The antiproliferative effects of phosphazenes (2, 2a, and 2b) on prostate (PC-3) and colon cancer (HT-29) cell lines were determined by cell viability analysis using MTT assay. Antimigratory effects were also investigated by scratch analysis. In addition, the effects of compounds against genes involved in apoptosis and cell migration were evaluated by gene expression analysis. As a result, it was found that compound 2a was more effective than compound 2b in both prostate and colon cancer cell lines. GRAPHICAL ABSTRACT