Synthesis, characterization, and assessment of cytotoxic, antiproliferative, and antiangiogenic effects of a novel procainamide hydrochloride-poly(maleic anhydride-co-styrene) conjugate


KARAKUŞ G. , Polat Z. A. , YAĞLIOĞLU A. Ş. , KARAHAN M., YENİDÜNYA A. F.

JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, cilt.24, ss.1260-1276, 2013 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 24 Konu: 10
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1080/09205063.2012.750209
  • Dergi Adı: JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
  • Sayfa Sayıları: ss.1260-1276

Özet

Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymerization reaction. A bioactive molecule, procainamide hydrochloride (PH), was then conjugated to MAST. The conjugation product was named as MAST/PH. Structural characterization of MAST and MAST/PH was carried out by Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. Their molecular weights were determined by size-exclusion chromatography. A mechanism was then suggested for the conjugation reaction. The results of the cytotoxicity assay, employing a mouse fibroblast cell line (L929), indicated that MAST/PH had no cytotoxicity at concentrations 62gmL(1) (p>0.05). Antiproliferative activities of MAST/PH and PH were determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. In the experiment, two anticancer chemotherapy drugs, cisplatin and 5-fluorouracil, were included as positive control. Antiproliferative activity results demonstrated that MAST/PH yielded the highest suppression profile (approximately 42%) at 20g/ml, while free PH exerted the same activity at 100g/ml. Interestingly, both MAST/PH and PH suppressed the proliferation of only one of the cell lines, C6 cells. Both cisplatin and 5-fluorouracil yielded approximately 60% antiproliferative activity on C6 cells at 20 and 100g/ml concentrations. Antiangiogenic capacity of both MAST and MAST/PH was also investigated by using the chicken chorioallantoic membrane assay. Results obtained indicated that while MAST/PH could be included into the category of good antiangiogenic substances, the activity score of MAST was within the weak category.