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


Binici A., ELMAS G., OKUMUŞ A., Erden Tayhan S., HÖKELEK T., Seker B. N. , ...More

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2021
  • Doi Number: 10.1080/07391102.2021.2006084
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: 4-Fluorobenzyl-spiro(N, O)cyclotriphosphazenes, spectroscopy, antimicrobial activity, DNA interactions, antiproliferative activity, antimigrative effect, DNA INTERACTIONS, INTERMOLECULAR INTERACTIONS, CYTOTOXIC ACTIVITIES, ELECTROCHEMICAL INVESTIGATIONS, ANTIMICROBIAL ACTIVITIES, STEREOGENIC PROPERTIES, QUANTITATIVE-ANALYSIS, HIRSHFELD SURFACES, ANTITUBERCULOSIS, SALTS
  • Hacettepe University Affiliated: Yes

Abstract

The starting compound, tetrachloro-4-fluorobenzyl-spiro(N/O)cyclotriphosphazene (2), was synthesized from the substitution reaction of hexachlorocyclotriphosphazatriene (N3P3Cl6; 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, H-1-, C-13- and P-31-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.