Antiproliferative Effects against A549, Hep3B and FL Cell Lines of Cyclotriphosphazene-Based Novel Protic Molten Salts: Spectroscopic, Crystallographic and Thermal Results

Okumus A., Akbas H., Karadag A., Aydin A., Kilic Z., HÖKELEK T.

CHEMISTRYSELECT, vol.2, no.18, pp.4988-4999, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 2 Issue: 18
  • Publication Date: 2017
  • Doi Number: 10.1002/slct.201700497
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4988-4999
  • Hacettepe University Affiliated: Yes


The protic molten salts (PMOS) of (1a-6b) have been prepared from the reactions of tetrapyrrolidino (1-3) and tetrapiperidino (4-6) fully substituted phosphazenes with the gentisic and gamma-resorcylic acids. The structures of PMOS (1a-6b) were characterized by elemental analyses, FTIR and H-1, C-13{H-1}, P-31{H-1} NMR techniques. The crystal structures of 1b and 2b were established by X-ray diffraction method. The thermal properties of PMOS were verified using thermogravimetric instruments. In addition, this study also focused on the pharmacological abilities of the PMOS to affect the cell growth and cell cytotoxicity on A549, Hep3B and normal human amnion (FL) cell lines and to interact with calf thymus DNA (CT-DNA). Studies on the cells displayed that these PMOS demonstrated significant antiproliferative effect in conjunction with caused apoptotic-like changes in morphology. The PMOS are able to strongly bind to CT-DNA through minor groove binding modes with hyperchromic effect. The IC50 and binding constant ranges of the PMOS were found to be as 25-160 mu M and 0.5 x 10(3) - 12.0 x 10(3) M-1, respectively. These findings indicate that the PMOS 1b-6b are more antiproliferative than those of the PMOS 1a-6a. Moreover, it is observed that the CT-DNA most significantly bound the PMOS 1b-6b. Consequently, a good correlation between the antiproliferative effects and their binding activities of these PMOS was observed.