title: Synthesis, characterization, and assessment of cytotoxic, antiproliferative, and antiangiogenic effects of a novel procainamide hydrochloride-poly(maleic anhydride-co-styrene) conjugate.
abstract: 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 [Formula: see text] 62 μg mL(-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 20 μg/ml, while free PH exerted the same activity at 100 μg/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 100 μg/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.
authors.affiliation: Research Center of the Cumhuriyet University School of Medicine, CUTFAM-RCCUSM, 58140, Sivas, Turkey. gulderen@cumhuriyet.edu.tr
authors.forename: Gulderen
authors.initials: G
authors.lastname: Karakus
authors.forename: Zubeyde
authors.initials: Z
authors.lastname: Akin Polat
authors.forename: Ayse
authors.initials: A
authors.lastname: Sahin Yaglıoglu
authors.forename: Mesut
authors.initials: M
authors.lastname: Karahan
authors.forename: Ali Fazil
authors.initials: AF
authors.lastname: Yenidunya
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D008299:Maleic Anhydrides / Q000737:chemistry*; D051379:Mice; D011108:Polymers / Q000737:chemistry*; D011342:Procainamide / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D008299:Maleic Anhydrides; D011108:Polymers; D011342:Procainamide