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 N¹,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

Keywords:

• Bis(2-furanylmethyl)spirocyclotriphosphazenes
• antimigratory acitivity
• antiproliferative activity
• colon cancer
• prostate cancer
• spectroscopy

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We would like to thank the Tokat Gaziosmanpaşa University Research Fund (TOGU-BAP: 2019/44) for financial support. T. H. is grateful to Hacettepe University Scientific Research Unit (Grant No. 013 D04 602 004).