Phosphorus-nitrogen compounds. Part 58. Syntheses, structural characterizations and biological activities of 4-fluorobenzyl-spiro(N/O)cyclotriphosphazene derivatives

• Published in: Journal of biomolecular structure & dynamics 2023-01, Vol.41 (1), p.298-318
• Main Authors: Binici, Arzu, Elmas, Gamze, Okumuş, Aytuğ, Erden Tayhan, Seçil, Hökelek, Tuncer, Şeker, Büşra Nur, Açık, Leyla, Kılıç, Zeynel
• Format: Article
• Language: English
• Subjects: 4-Fluorobenzyl-spiro(N/O)cyclotriphosphazenes; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antimicrobial activity; antimigrative effect; antiproliferative activity; Crystallography, X-Ray; DNA - chemistry; DNA interactions; Nitrogen - chemistry; Nitrogen Compounds - chemistry; Phosphorus - chemistry; spectroscopy
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.2006084

The starting compound, tetrachloro-4-fluorobenzyl-spiro(N/O)cyclotriphosphazene (2), was synthesized from the substitution reaction of hexachlorocyclotriphosphazatriene (N 3 P 3 Cl 6 ; trimer; HCCP) with sodium 3-(4-fluorobenzylamino)-1-propanoxide (1). Reactions of spiro (2) with excess 1-(2-aminoethyl)-piperidine, 4-(2-aminoethyl)-morpholine, 1-(2-hydroxyethyl)piperidine and 4-(2-aminoethyl)morpholine yielded the fully substituted cyclotriphosphazene derivatives (2a-2d), respectively. Elemental analysis, mass spectrometry (ESI-MS), FTIR, 1 H-, 13 C- and 31 P-NMR data confirmed the structure of the new cyclotriphosphazenes (2a-2d); and the crystal structure of 2 was also identified by X-ray crystallography. The quantum mechanical DFT calculations of 2 were performed to estimate the geometry optimization, total energy, orientation of frontier molecular orbitals (HOMOs and LUMOs), and chemical parameters. In addition, antibacterial and antifungal activities of the fully substituted 4-fluorobenzyl-spiro(N/O)cyclotriphosphazenes (2a-2d) were investigated against G(+) and G(−) bacteria and fungi. Using agarose gel electrophoresis, the DNA cleavage activities of these phosphazenes on double-stranded plasmid DNA were evaluated. To evaluate the abilities of compounds 2a-2d to inhibit cell proliferation in different concentrations, the antiproliferative and antimigrative activities against prostate adenocarcinoma (PC3), breast cancer (MCF7) and colon cancer (HT29) cell lines were studied in vitro; and the compound 2c was determined to be the most efficient against the three cancer cells. Communicated by Ramaswamy H. Sarma