5-氟尿嘧啶修饰卟啉的合成及抗肿瘤活性

doi:10.11944/j.issn.1000-0518.2016.12.160054

摘要/Abstract

摘要：

合成了一种5-氟尿嘧啶修饰的自由卟啉(5-[2-(5-氟尿嘧啶-3-基)乙氧基苯基]-10,15,20-三(4-甲氧基苯基)卟啉)及其2种金属卟啉配合物:5-[2-(5-氟尿嘧啶-3-基)乙氧基苯基]-10,15,20-三(4-甲氧基苯基)锰卟啉和5-[2-(5-氟尿嘧啶-3-基)乙氧基苯基]-10,15,20-三(4-甲氧基苯基)锌卟啉。通过紫外可见光谱(UV-Vis)、红外光谱(IR)和核磁共振谱氢谱(¹H NMR)对目标化合物进行了结构表征。用噻唑蓝法(MTT法)测定了自由卟啉、锰卟啉及锌卟啉分别对肺腺癌细胞株A549、肝癌细胞株Bel7402和人结肠癌细胞株HCT-8的抑制活性。其中,锰卟啉对人结肠癌细胞株HCT-8的半抑制浓度为IC₅₀为17.8 mg/L,具有一定的细胞毒作用。

关键词: 卟啉, 氟尿嘧啶, 抗肿瘤活性

Abstract:

The porphyrin modified with 5-fluorouracil(5-[2-(5-fluorouracil-3-yl)-ethoxyphenyl]-10,15,20-tri(4-methoxyphenyl) porphyrin) and its two metal porphyrin complexes: 5-[2-(5-fluorouracil-3-yl)-ethoxyphenyl]-10,15,20-tri(4-methoxyphenyl) Mn porphyrin and 5-[2-(5-fluorouracil-3-yl)-ethoxyphenyl]-10,15,20-tri(4-methoxyphenyl) Zn porphyrin were synthesized. The structures of the three compounds were characterized by ultraviolet visible spectroscopy(UV-Vis), infred spectroscopy(IR) and proton nuclear magnetic resonance spectroscopy(¹H NMR). The antitumor activities of these compounds to A549, Bel7402, HCT-8 were tested using the methyl thiazolyl tetrazolium(MTT) method. The results show that the IC₅₀ value of Mn porphyrin to HCT-8 is 17.8 mg/L.

Key words: porphyrin, fluorouracil, antitumor activity

任丽磊, 彭晓霞, 赵秀丽, 祝红梅. 5-氟尿嘧啶修饰卟啉的合成及抗肿瘤活性[J]. 应用化学, 2016, 33(12): 1415-1419.

REN Lilei, PENG Xiaoxia, ZHAO Xiuli, ZHU Hongmei. Synthesis and Antitumor Activity of Porphyrin Modified with 5-Fluorouracil[J]. Chinese Journal of Applied Chemistry, 2016, 33(12): 1415-1419.

参考文献

[1]	Li M,Zhang J,Feng L,et al. The In Vitro Anti-tumor Efficacy and the Pharmacokinetics of N3-o-toluylfluorouracil Loaded Nanosuspension(TFu-LNS)[J]. J Biomed Nanotechnol,2013,9(5):801-810.
[2]	Sun W T,Zhang N,Li X. Release Mechanism Studies on TFu Nanoparticles-in-microparticles System[J]. Colloids Surf B,2012,95(6):115-120.
[3]	TONG Chunyi,TANG Fengxia,LIU Bin,et al. Preparation of Micro-spheres Co-carried Anti-tumor Drug and Sensitizer(5-Fu-COS/SeNP) and Their Inhibiting Tumorous Cellular Growths Activity[J]. Chem J Chinese Univ,2014,35(7):1603-1607(in Chinese). 童春义,唐凤霞,刘斌,等. 氟尿嘧啶-壳寡糖/硒纳米微球的制备及抑制肿瘤细胞生长活性[J]. 高等学校化学学报,2014,35(7):1603-1607.
[4]	LIU Yanqin,ZHANG Huijuan,HAN Shitian. Synthesis and Antitumor Activity of 5-Fluorouracil-porphyrin Compounds[J]. Chinese J Org Chem,2002,22(4):279-282(in Chinese). 刘彦钦,张慧娟,韩士田. 5-氟尿嘧啶-卟啉化合物的合成及抗癌活性[J]. 有机化学,2002,22(4):279-282.
[5]	HAN Junxing,LIU Yanqin,HAN Shitian. Synthesis of m-Chlorophenyl Mn-porphyrin-5-Fluorouracil Complexes and Their Inhibition Activity to Cancer Cells[J]. Chinese J Appl Chem,2012,29(6):718-720(in Chinese). 韩军兴,刘彦钦,韩士田. 间氯苯基锰卟啉-5-氟尿嘧啶配合物的合成及其对癌细胞的抑制活性[J]. 应用化学,2012,29(6):718-720.
[6]	PENG Yuling,WANG Shujun,FU Li,et al. Synthesis of Tailed Porphyrin Modified with Nicotinic Acid and Interactions with Human Serum Albumin[J]. Acta Phys-Chim Sin,2012,28(5):1054-1062(in Chinese). 彭玉苓,王树军,傅丽,等. 烟酸修饰尾式卟啉的合成及其与人血清白蛋白的相互作用[J]. 物理化学学报,2012,28(5):1054-1062.
[7]	Gouterman M. Spectra of Porphyrins[J]. J Mol Spectrosc,1961,6:138-163.
[8]	SUN Erjun,WANG Dong,CHENG Xiuli,et al. Preparation and Properties of 5,10,15,20-Tetra(4-myristylimidophenyl) Porphyrin and Its Zn and Mn Complexes[J]. Chem J Chinese Univ,2007,28(7):1208-1213(in Chinese). 孙二军,王栋,程秀利,等. 5,10,15,20-四(对-十四酰亚胺基苯基)卟啉及其锰、锌配合物的合成及性质[J]. 高等学校化学学报,2007,28(7):1208-1213.
[9]	ZHAO Shengfang,CHEN Nianyou,XIA Jingping,et al. Microwave Synthesis and Spectroscopic Property of Tetra(2-hydroxphenyl) Porphyrin and Its Matal Complexes[J]. J Wuhan Univ Technol,2013,35(11):43-46(in Chinese). 赵胜芳,陈年友,夏静平,等. 四(2-羟基苯基)卟啉及系列金属配合物的微波合成和光谱性质[J]. 武汉理工大学学报,2013,35(11):43-46.
[10]	YANG Qiuqing,HAN Shitian,ZHANG Huijuan. Spectral and Antitumor Activity Studies of Tail-porphyin-5-Fluorouracil and Their Metallic Manganese Complexes[J]. Chinese J Anal Chem,2001,29(12):1379-1383(in Chinese). 杨秋青,韩士田,张慧娟. 尾式卟啉-5-氟尿嘧啶及其金属络合物的光谱分析[J]. 分析化学,2001,29(12):1379-1383.
[11]	LI Meirong,CAI Xiaoqing,ZHU Yifeng,et al. Synthesis and Biological Evaluation of Novel Coupling Derivatives of Photosensitizer and 5-Fluorouracil as Antineoplastic Agents[J]. Acta Chim Sin,2011,69(4):425-430(in Chinese). 李美容,蔡晓庆,朱易峰,等. 5-氟尿嘧啶光敏性偶联衍生物的合成、表征及抗癌活性研究[J]. 化学学报,2011,69(4):425-430.

[1]	王小梅, 郭江飞, 王立志, 黄健涵. 卟啉基超交联聚合物的合成及其对二氧化碳和汞（Ⅱ）离子的吸附[J]. 应用化学, 2022, 39(7): 1083-1089.
[2]	张艺潆, 李翠艳, 赵杰, 余笑明, 方千荣. 卟啉-硫醚基共价有机框架材料用于氧还原反应电催化剂[J]. 应用化学, 2022, 39(4): 647-656.
[3]	张会丽, 崔红艳, 黄文龙, 胡国强. 饶丹宁甲叉基取代左氧氟沙星衍生物的合成与抗肿瘤活性[J]. 应用化学, 2021, 38(2): 188-194.
[4]	武彧, 刘家成. 倒插式配位自组装染料敏化太阳能电池的制备与表征[J]. 应用化学, 2021, 38(11): 1494-1502.
[5]	吴学姣, 苟光淋, 杨小兰, 杨家强. 二肽类膦酸酯衍生物的合成与抗肿瘤活性[J]. 应用化学, 2021, 38(1): 36-43.
[6]	张思佳, 徐彩娜, 陈杰, 田华雨, 陈学思. 通过调控肿瘤代谢增强T细胞抗肿瘤活性[J]. 应用化学, 2020, 37(9): 977-984.
[7]	王禹婷,杨天怡,章应辉. 卟啉框架材料在光催化领域的应用[J]. 应用化学, 2020, 37(6): 611-619.
[8]	郭洪辰, 秦玉升, 王献红. 乙酸/氧气法高效合成取代卟啉[J]. 应用化学, 2020, 37(3): 264-270.
[9]	张会丽, 崔红艳, 黄文龙, 胡国强. 左氧氟沙星3-芳苄叉基-喹啉-4-酮衍生物的合成及抗肿瘤活性[J]. 应用化学, 2020, 37(12): 1426-1431.
[10]	宫益林, 史建涛, 王洋, 陈烨, 丁实, 刘洋, 刘举. 新型吲唑-查尔酮杂合物的合成及抗肿瘤活性[J]. 应用化学, 2019, 36(9): 1015-1022.
[11]	张会丽, 李珂, 黄文龙, 王蕊, 胡国强. N-(5-芳苄叉基饶丹宁)左氧氟沙星酰胺的合成及抗肿瘤活性[J]. 应用化学, 2019, 36(8): 897-903.
[12]	李元元,张呈霞,黄文龙,陈超然,胡国强. 左氧氟沙星的噻唑并均三唑衍生物的合成及抗肿瘤活性[J]. 应用化学, 2019, 36(6): 671-676.
[13]	陈川,徐迎迪,薛叙明,周鹏鹏. 金属卟啉/MgAl水滑石催化醇选择性氧化制备羰基化合物[J]. 应用化学, 2019, 36(11): 1286-1293.
[14]	郭洪辰, 秦玉升, 王献红, 王佛松. 铝卟啉配合物催化二氧化碳与环氧丙烷共聚反应[J]. 应用化学, 2019, 36(10): 1118-1127.
[15]	桂舒雅,熊昊,林智,夏霖亚,钟启升,李东风,侯瑞斌,夏艳. 新型含有金刚烷苯乙烯结构单元化合物的合成和初步抗肿瘤增殖[J]. 应用化学, 2018, 35(4): 420-425.