The first peptide derivatives of dioxybiphenyl-bridged spiro cyclotriphosphazenes: In vitro cytotoxicity activities and DNA damage studies

Koran K., Çalışkan E., Altay Öztürk D., ÇAPAN İ., TEKİN S., SANDAL S., ...Daha Fazla

Bioorganic Chemistry, cilt.132, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 132
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.bioorg.2022.106338
  • Dergi Adı: Bioorganic Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Veterinary Science Database
  • Anahtar Kelimeler: Cyclotriphosphazene, DNA damage, Phosphazene, Dipeptide, Cytotoxicity, PHOSPHAZENE HIGH POLYMERS, ANTITUMOR-ACTIVITY, SUBSTITUTED CYCLOTRIPHOSPHAZENES, THERMAL CHARACTERIZATIONS, AMINO, FABRICATION, PROFILES, AMYLOIDS, BEARING, DESIGN
  • Marmara Üniversitesi Adresli: Evet

Özet

In this study, we aimed to synthesize new peptide-substituted cyclotriphosphazenes from a series of tyrosine-based peptides and dioxyphenyl-substituted spirocyclotriphosphazenes, and to evaluate their in vitro cytotoxicity and genotoxicity activities. Genotoxicity studies were conducted to understand whether the cytotoxic compounds cause cell death through DNA damage. The structures of the novel series of phosphazenes were characterized by FT-IR, elemental analysis, MS, 1D (31P, 1H, and 13C-APT NMR), and 2D (HETCOR) NMR spectroscopic techniques. In vitro cytotoxic activities were carried out against human breast (MCF-7), ovarian (A2780), prostate (PC-3), colon (Caco-2) cancer cell lines and human normal epithelial cell line (MCF-10A) at different concentrations by using an MTT assay. The compounds showed considerable reductions in cell viability against all human cancer cell lines. Especially, the compounds exhibited notable effects in A2780 cell lines (p < 0.05). The IC50 values of the compounds in the A2780 cell line were calculated to be 1.914 µM for TG, 20.21 µM for TV, 20.45 µM for TA, 4.643 µM for TP, 5.615 µM for BTG, 1.047 µM for BTV, 27.02 µM for BTA, 0.7734 µM for BTP, 21.5 µM for DTG, 1.65 µM for DTV, 2.89 µM for DTA and 4.599 µM for DTP. DNA damage studies of the compounds were conducted by the comet assay method using tail length, tail density, olive tail moment, head length, and head density parameters, and the results showed that the cell death occurred through DNA damage mechanism. In a nutshell, these compounds show promising cytotoxic effects and can be considered powerful candidate molecules for pharmaceutical applications.