巯基化阿霉素的两种合成方法的比较

吴珊; 张叶叶; 郭海霞; 刘俊杰; 孙治国; 钟延强; 邹豪

doi:10.3969/j.issn.1006-0111.2014.06.008

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

x 关闭永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

巯基化阿霉素的两种合成方法的比较

吴珊, 张叶叶, 郭海霞, 刘俊杰, 孙治国, 钟延强, 邹豪

文章导航 > 药学实践与服务 > 2014 > 32(6): 428-433

吴珊, 张叶叶, 郭海霞, 刘俊杰, 孙治国, 钟延强, 邹豪. 巯基化阿霉素的两种合成方法的比较[J]. 药学实践与服务, 2014, 32(6): 428-433. doi: 10.3969/j.issn.1006-0111.2014.06.008

引用本文:

WU Shan, ZHANG Yeye, GUO Haixia, LIU Junjie, SUN Zhiguo, ZHONG Yanqiang, ZOU Hao. A comparison study of synthesizing methods of thiolated doxorubicin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(6): 428-433. doi: 10.3969/j.issn.1006-0111.2014.06.008

Citation:

WU Shan, ZHANG Yeye, GUO Haixia, LIU Junjie, SUN Zhiguo, ZHONG Yanqiang, ZOU Hao. A comparison study of synthesizing methods of thiolated doxorubicin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(6): 428-433. doi: 10.3969/j.issn.1006-0111.2014.06.008

巯基化阿霉素的两种合成方法的比较

doi: 10.3969/j.issn.1006-0111.2014.06.008

1.
第二军医大学药学院药剂学教研室, 上海 200433
2.
解放军266医院, 河北承德 067000

基金项目: 国家自然科学基金项目(30801441);科技部重大新药创制专项(2014ZX09J14107-01B).

A comparison study of synthesizing methods of thiolated doxorubicin

1.
Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2.
NO.266 Hospital of PLA, Chengde 067000, China

摘要: 目的探索合成供金纳米粒载药系统研究用模型药物巯基化阿霉素的可行方法。方法分别采用2-亚氨基硫烷盐酸盐(2-IT)法和琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)法合成巯基阿霉素,通过高效液相色谱(HPLC)、飞行时间质谱(MS-ESI)及核磁共振氢谱(¹H NMR)验证巯基阿霉素的合成,并考察反应物摩尔比、反应时间等因素对合成巯基阿霉素的影响。结果 ¹H NMR 确证DOX-SATA出现了与硫酯基团相连的质子信号,表明新合成的化合物中含有硫酯基团。HPLC及MS-ESI结果显示,两种方法均能合成巯基阿霉素,2-IT法生成的巯基阿霉素,随着反应时间延长易发生环化,形成环化巯基阿霉素。SATA试剂法合成巯基阿霉素过程中不易发生副反应,合成的巯基阿霉素较为稳定。结论通过两种方法的比较,SATA法合成巯基阿霉素的方法较为可行。
- 巯基化阿霉素 /
- 2-亚氨基硫烷盐酸盐(2-IT) /
- 琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)
Abstract: Objective To investigate the optimal method for synthesizing thiolated doxorubicin. Methods Thiolated doxorubicin was synthesized through two different methods. Doxorubicin was reacted with 2-iminothiolane (2-IT) and S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA),respectively. The synthesized thiolated doxorubicin was further characterized by HPLC and MS-ESI techniques. Several factors including molar ratios as well as reaction time were evaluated. Results The results showed that thiolated doxorubicin could be synthesized via both of the two methods successfully. Thiolated doxorubicin could be stable when doxorubicin was reacted with SATA. But the crude thiolated doxorubicin could be cyclized easily when doxorubicin was reacted with 2-IT. Conclusion Thiolated doxorubicin prepared with SATA is more feasible than that with 2-IT.
- thiolated doxorubicin /
- 2-iminothiolane (2-IT) /
- S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA)

[1]	Li PY, Lai PS, Hung WC, et al. Poly(l-lactide)-vitamin E TPGS nanoparticles enhanced the cytotoxicity of doxorubicin in drug-resistant MCF-7 breast cancer cells[J].Biomacromolecules 2010,11(10):2576-2582.
[2]	Kibria G, Hatakeyama H, Harashima H.Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system[J].Arch Pharm Res, 2014, 37(1): 4-15.
[3]	Thierry AR, Vige D, Coughlin SS, et al. Modulation of doxorubicin resistance in multidrug-resistant cells by liposomes[J].FASEB J, 1993,7(6):572-579.
[4]	Kumar SA, Peter YA, Nadeau JL. Facile biosynthesis, separation and conjugation of gold nanoparticles to doxorubicin[J].Nanotechnology,2008,10(49):495101.
[5]	Barraud L, Merle P, Soma E, et al. Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo[J].J Hepatol 2005,42(5):736-743.
[6]	Ma P, Mumper RJ. Anthracycline nano-delivery systems to overcome multiple drug resistance: a comprehensive review[J].Nano Today,2013,8(3):313-331.
[7]	Wang X, Cai X, Hu J, et al. Glutathione-triggered "off-on" release of anticancer drugs from dendrimer-encapsulated gold nanoparticles[J].J Am Chem Soc 2013,135(26):9805-9810.
[8]	Gu YJ, Cheng J, Man CW, et al. Gold-doxorubicin nanoconjugates for overcoming multidrug resistance[J]. Nanomedicine, 2012,8(2):204-211.

[1]	郭灵怡, 刘艳超, 高路, 刘瑞瑶, 吕权真, 俞媛. 醋酸卡泊芬净单硬脂酸甘油酯纳米粒抗白色念珠菌感染的增效作用研究 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202310043
[2]	陈炳辰, 王思真, 郭贝贝, 杨峰. 紫杉醇棕榈酸酯的合成及其脂质体的制备与处方研究 . 药学实践与服务, 2024, 42(9): 379-384, 410. doi: 10.12206/j.issn.2097-2024.202404062
[3]	崔亚玲, 吴琼, 马良煜, 胡北, 姚东, 许子华. 肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯皮肤药动学研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404006
[4]	毛智毅, 王筱燕, 陈晓颖, 汤逸斐. 度拉糖肽联合二甲双胍对肥胖型2型糖尿病患者机体代谢、体脂成分及血清脂肪因子的影响 . 药学实践与服务, 2024, 42(7): 305-309. doi: 10.12206/j.issn.2097-2024.202305032
[5]	陈炳辰, 佟达丰, 万苗, 闫飞虎, 姚建忠. UPLC-MS/MS法测定小鼠血浆中紫杉醇脂肪酸酯前药及其药代动力学研究 . 药学实践与服务, 2024, 42(8): 341-345. doi: 10.12206/j.issn.2097-2024.202404082
[6]	邹思, 吴岩斌, 吴锦忠, 吴建国, 黄家兴. 虎奶菇菌核多糖功能化纳米硒抗疲劳功效研究 . 药学实践与服务, 2024, 42(10): 426-432. doi: 10.12206/j.issn.2097-2024.202206072
[7]	桂明珠, 李静, 李志玲. 儿童伏立康唑的血药浓度与CYP2C19、CYP2C9和CYP3A5基因多态性的相关性研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402020

点击查看大图

计量

文章访问数: 4470
HTML全文浏览量: 376
PDF下载量: 713
被引次数: 0

巯基化阿霉素的两种合成方法的比较

doi: 10.3969/j.issn.1006-0111.2014.06.008

1. 第二军医大学药学院药剂学教研室, 上海 200433

2. 解放军266医院, 河北承德 067000

基金项目: 国家自然科学基金项目(30801441);科技部重大新药创制专项(2014ZX09J14107-01B).

收稿日期: 2014-08-02
修回日期: 2014-10-13

关键词:

巯基化阿霉素 /

2-亚氨基硫烷盐酸盐(2-IT) /

琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)

摘要: 目的探索合成供金纳米粒载药系统研究用模型药物巯基化阿霉素的可行方法。方法分别采用2-亚氨基硫烷盐酸盐(2-IT)法和琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)法合成巯基阿霉素,通过高效液相色谱(HPLC)、飞行时间质谱(MS-ESI)及核磁共振氢谱(¹H NMR)验证巯基阿霉素的合成,并考察反应物摩尔比、反应时间等因素对合成巯基阿霉素的影响。结果 ¹H NMR 确证DOX-SATA出现了与硫酯基团相连的质子信号,表明新合成的化合物中含有硫酯基团。HPLC及MS-ESI结果显示,两种方法均能合成巯基阿霉素,2-IT法生成的巯基阿霉素,随着反应时间延长易发生环化,形成环化巯基阿霉素。SATA试剂法合成巯基阿霉素过程中不易发生副反应,合成的巯基阿霉素较为稳定。结论通过两种方法的比较,SATA法合成巯基阿霉素的方法较为可行。