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Research on Chemical Intermediates

, Volume 42, Issue 5, pp 4221–4251 | Cite as

Phosphorus–nitrogen compounds part 33: in vitro cytotoxic and antimicrobial activities, DNA interactions, syntheses, and structural investigations of new mono(4-nitrobenzyl)spirocyclotriphosphazenes

  • Aytuğ Okumuş
  • Hüseyin Akbaş
  • Zeynel Kılıç
  • L. Yasemin Koç
  • Leyla Açık
  • Betül Aydın
  • Mustafa Türk
  • Tuncer Hökelek
  • Hakan Dal
Article

Abstract

The condensation reactions of hexachlorocyclotriphosphazene, N3P3Cl6, with N-alkyl-N′-mono(4-nitrobenzyl)diamines (13), NO2PhCH2NH(CH2) n NHR1 (R1 = CH3 or C2H5), led to the formation of the mono(4-nitrobenzyl)spirocyclotriphosphazenes (46). The tetra-pyrrolidino (4a6a), piperidino (4b6b), and 1,4-dioxa-8-azaspiro[4,5]decaphosphazenes (4c6c) were prepared from(for) the reactions of partly substituted compounds (4, 5, and 6) with excess pyrrolidine, piperidine, and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), respectively. The partly substituted geminal (4d and 5d) and cis-morpholino (6d) phosphazenes were isolated from the reactions of excess morpholine in boiling THF and o-xylene, but the expected fully substituted compounds were not obtained. The structures of all the phosphazene derivatives were determined by elemental analyses, MS, FTIR, 1H, 13C{1H}, 31P{1H} NMR, HSQC, and HMBC techniques. The crystal structures of 4, 6, 4a, and 5a were verified by X-ray diffraction analysis. In addition, in vitro cytotoxic activities of fully substituted phosphazenes (4a6c) against HeLa cervical cancer cell lines (ATCC CCL-2) and the compounds 4a and 4c against breast cancer cell lines (MDA-MB-231) and L929 fibroblast cells were evaluated, respectively. Apoptosis effect was determined by MDA-MB-231 cancer cell lines and fibroblast cells. The MIC values of the compounds were in the ranges of 9.8–19.5 µM. The compounds 6, 5a, 6a, 5b, and 6d have greater MIC activity against bacterial and yeast strain. The investigation of DNA binding with the phosphazenes was studied using plasmid DNA. The phosphazene derivatives inhibit the restriction endonuclease cleavage of plasmid DNA by BamHI and HindIII enzymes. BamHI and HindIII digestion results demonstrate that the compounds bind with G/G and A/A nucleotides.

Keywords

Spirocyclotriphosphazenes Spectroscopy Crystal structure Cytotoxicity Breast and HeLa cancer cell lines DNA interactions 

Notes

Acknowledgments

The authors acknowledge the “Ankara University, Scientific Research Unit” Grant No. 09B4240006. T. H. is grateful to Hacettepe University Scientific Research Project Unit (Grant No. 013 D04 602 004) and Z. K. thanks the Turkish Academy of Sciences (TÜBA) for partial support of this work.

Supplementary material

11164_2015_2271_MOESM1_ESM.doc (8.2 mb)
Supplementary material 1 (DOC 8433 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Aytuğ Okumuş
    • 1
  • Hüseyin Akbaş
    • 2
  • Zeynel Kılıç
    • 1
  • L. Yasemin Koç
    • 3
  • Leyla Açık
    • 4
  • Betül Aydın
    • 4
  • Mustafa Türk
    • 5
  • Tuncer Hökelek
    • 6
  • Hakan Dal
    • 7
  1. 1.Department of ChemistryAnkara UniversityAnkaraTurkey
  2. 2.Department of ChemistryGaziosmanpaşa UniversityTokatTurkey
  3. 3.The Turkish Sugar AuthorityAnkaraTurkey
  4. 4.Department of BiologyGazi UniversityAnkaraTurkey
  5. 5.Department of BioengineeringKırıkkale UniversityKirikkaleTurkey
  6. 6.Department of PhysicsHacettepe UniversityAnkaraTurkey
  7. 7.Department of ChemistryAnadolu UniversityEskisehirTurkey

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