Zakir M.o. RZAYEV, Mustafa TÜRK, Gülten KAHRAMAN, Erhan PİŞKİN

Biyomühendislik Fonksiyonel Kopolimerler. XIX. Anhidrit- Organobor Fonksiyonlu Kopolimerlerin Sentezi ve Kanser Hücreleriyle Etkileşimleri

Maleik anhidritin homo- ve kopolimerlerinin yeni biyomühendislik fonksiyonel türevlerinin senthezi, 1 anhidrit-içeren makromoleküllerin [poli MA-alt-methyl vinil eter MVE biyomühendislik polimeri] 2-aminoetildifenillborinat 2-AEPB ile amidolizi, 2 alfa-hidroksi-omega-metoksi-polietilen oksit PEO uyumluluk ajanı ile esterleşmesi ve 3 organaoboron PEO içeren kopolimerlerin folik asit gibi hedefleyici ajanla konjugasyonu gibi yöntemlerle gerçekleştirilmiştir. Sentezlenmiş oligomerlerin yapısı ve kompozisyonu FTIRATR ve 1H 13C NMR spectroskopisi ile karakterize edilmiştir. Organobor fonksiyonal kopolimerlerin antitümör aktivitesi sitotoksisite, istatistiksel, ikili boyama ve immün boyama ile apoptotik ve nekrotik hücre indeksi, ışık ve floresan inverted mikroskop analizi gibi çeşitli fiziksel ve biyokimyasal kombine yöntemler ile araştırılmıştır. Organoboron makromoleküllerinin sitotoksik ve apoptotik/nekrotik etkisi önemli ölçüde kopolimerlerin yapısına ve kompozisyonuna bağlı olduğu bulunmuştur. Sentezlenmiş bazı kopolimerlerin 400 g.mL-1 derişim değerinde normal hücrelere düşük toksik, kanser hücrelerine ise etkili terapötik ilaç etksi göstermiştir

Anahtar Kelimeler:

Organobor polimerleri, yapı-özellik ilişkileri, sitotoksisite, nekrotik ve apoptotik etki, kanser hücreleri

Bioengineering Functional Copolymers. XIX. Synthesis of Anhydride-Organoboron Functionalized Copolymers and Their Interaction with Cancer Cells

Novel bioengineering functional organoboron homo- and copolymer of maleic anhydride MA were synthe- sized by 1 amidolysis of anhydride-containing macromolecules [poly MA-alt-methyl vinyl ether MVE as a bioengineering polymer] with 2-aminoethyldiphenylborinate 2-AEPB , 2 esterification with α-hydroxy-ω-methoxy-poly ethylene oxide PEO as a compatibilizer and 3 conjugation of organoboron PEO branches with folic acid as a targetting agent. Structure and composition of the synthesized oligomers were characterized by FTIR-ATR and 1H 13C NMR spectroscopy. Antitumor activity of the organoboron functional co polymers were investigated by a combination of various physical and biochemical methods such as cytotoxicity, statistical, apoptotic and necrotic cell indexes, double staining and caspase-3 immunostaining, light and fluorescence inverted microscope analyses. It was found that cytotoxicity and apoptotic/necrotic effects of organoboron macromolecules significantly depend on the structure and composition of studied co polymers. Some synthesized co polymers at 400 μg.mL-1 concentration as a therapeutic drug exhibits minimal toxicity toward the normal cells, but influential for cancer cells.

Keywords:

Organoboron polymers, structure-property relations, cytotoxicity, necrotic and apoptotic effects, cancer cells,

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