Synthesis, characterization and antiproliferative activities of novel modified poly (maleic anhydride-co-vinyl acetate)/cytosine beta-D-arabinofuranoside hydrochloride conjugate


KARAKUŞ G. , YAĞLIOĞLU A. Ş. , Zengin H. B. , KARAKUŞ N.

MARMARA PHARMACEUTICAL JOURNAL, vol.19, no.1, pp.73-81, 2015 (Journal Indexed in ESCI) identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 1
  • Publication Date: 2015
  • Title of Journal : MARMARA PHARMACEUTICAL JOURNAL
  • Page Numbers: pp.73-81

Abstract

Poly (maleic anhydride-co-vinyl acetate) (MAVA) copolymer was synthesized by free-radical-polymerization reaction in methyl ethyl ketone (MEK) at 80 degrees C using benzoyl-peroxide (BPO) as the radical-initiator. MAVA was then modified with anti-leukemic chemotherapy-agent cytosine beta-D-arabinofuranoside hydrochloride (CF). Modification was performed at 70 degrees C in dimethylformamide (DMF) containing triethylamine (Et3N) as the catalyst. Structural characterization of the copolymer and copolymer/drug couple (MAVA/CF) was carried out by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (H-1-NMR). FTIR and H-1-NMR spectra confirmed the modification reaction. UV-Spectrophotometric measurements indicated that MAVA/CF kept its molecular integrity in physiological-body-fluid, PBS, for first four days. Antiproliferative activities of MAVA/CF were also determined by BrdU-cell-proliferation-ELISA assays using C6 and HeLa cell lines (cisplatin and 5-fluorouracil used as positive control). MAVA/CF appeared to have little antiproliferative activity against C6 cell line while samples didn't have antiproliferative activity against HeLa cell line at low concentrations (<100 mu g/ml). Reaction mechanism was also recommended for modification product MAVA/CF.