Department of Biology, Faculty of Science and Art, Kirikkale University, Turkey.
Bioorg Med Chem. 2010 Nov 15;18(22):7975-84. doi: 10.1016/j.bmc.2010.09.031. Epub 2010 Sep 22.
Novel antitumor active functional polymers with supramacromolecular structures were synthesized by a complex-radical terpolymerization of N-isopropylacrylamide (NIPAm), 3,4-dihydro-2H-pyran (DHP), and maleic anhydride (MA) with 2,2'-azoisobisbutyronitrile as a radical initiator in 1,4-dioxane at 65°C under nitrogen atmosphere. The structure and composition of terpolymers were investigated by (1)H ((13)C) NMR spectroscopy. Interaction of terpolymers with human lung small cell carcinoma (SCLC) were investigated by using different methods such as cytotoxicity, statistical, apoptotic and necrotic cell indexes, double staining and caspase-3 immunostaining, light and fluorescence inverted microscopy analyses. Investigations into structure, composition, and antitumor activity relationships revealed that terpolymers containing a combination of ionisable amide-pyran linkages and H-bonded carboxylic groups exhibited higher cytotoxicity. It was observed that terpolymer with nearly alternating structure provides a maximum concentration of ionisable and H-bonded antitumor sites, and therefore, exhibits higher in vitro cytotoxicity, apoptotic and necrotic effects towards SCLC cancer cells.
采用 2，2′-偶氮二异丁腈（AIBN）为自由基引发剂，在氮气氛围下于 65°C 的 1，4-二氧六环中通过 N-异丙基丙烯酰胺（NIPAm）、3，4-二氢-2H-吡喃（DHP）和马来酸酐（MA）的复合自由基共聚反应，合成了具有超分子结构的新型抗肿瘤活性功能聚合物。通过（1）H（（13）C）NMR 光谱对共聚物的结构和组成进行了研究。采用细胞毒性、统计、凋亡和坏死细胞指数、双染色和 caspase-3 免疫染色、光和荧光倒置显微镜分析等不同方法研究了共聚物与人类小细胞肺癌（SCLC）的相互作用。结构、组成和抗肿瘤活性关系的研究表明，含有可离子化酰胺-吡喃键和氢键羧酸基团的共聚物具有更高的细胞毒性。结果表明，具有近乎交替结构的共聚物提供了最大浓度的可离子化和氢键抗肿瘤部位，因此对 SCLC 癌细胞表现出更高的体外细胞毒性、凋亡和坏死作用。
