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β-氨基酸聚合物用于协同增效逆转白色念珠菌对伊曲康唑的耐药性

马凯茜 张东辉 施超 顾佳蔚 刘润辉

马凯茜, 张东辉, 施 超, 顾佳蔚, 刘润辉. β-氨基酸聚合物用于协同增效逆转白色念珠菌对伊曲康唑的耐药性[J]. 功能高分子学报,2022,35(6):532-539 doi: 10.14133/j.cnki.1008-9357.20220403001
引用本文: 马凯茜, 张东辉, 施 超, 顾佳蔚, 刘润辉. β-氨基酸聚合物用于协同增效逆转白色念珠菌对伊曲康唑的耐药性[J]. 功能高分子学报,2022,35(6):532-539 doi: 10.14133/j.cnki.1008-9357.20220403001
MA Kaiqian, ZHANG Donghui, SHI Chao, GU Jiawei, LIU Runhui. Synergistic Effect of β-Amino Acid Polymers and Itraconazole on Reversing Drug Resistance in C. albicans[J]. Journal of Functional Polymers, 2022, 35(6): 532-539. doi: 10.14133/j.cnki.1008-9357.20220403001
Citation: MA Kaiqian, ZHANG Donghui, SHI Chao, GU Jiawei, LIU Runhui. Synergistic Effect of β-Amino Acid Polymers and Itraconazole on Reversing Drug Resistance in C. albicans[J]. Journal of Functional Polymers, 2022, 35(6): 532-539. doi: 10.14133/j.cnki.1008-9357.20220403001

β-氨基酸聚合物用于协同增效逆转白色念珠菌对伊曲康唑的耐药性

doi: 10.14133/j.cnki.1008-9357.20220403001
基金项目: 国家自然科学基金(22075078, 21861162010);上海市优秀学术带头人(20XD1421400)
详细信息
    作者简介:

    马凯茜(1996—),女,硕士生,研究方向为生物医用高分子材料。E-mail:ma05102022@163.com

    通讯作者:

    刘润辉, E-mail:rliu@ecust.edu.cn

  • 中图分类号: R318.08

Synergistic Effect of β-Amino Acid Polymers and Itraconazole on Reversing Drug Resistance in C. albicans

  • 摘要: 设计合成了与伊曲康唑具有协同活性的系列β-氨基酸聚合物。通过β-氨基酸N-硫代羧基酸酐(β-NTA)开环聚合的方法,将不同比例疏水性单体DL-β-正亮氨酸N-羧基硫代羰基环内酸酐(简称Bu)和阳离子单体N(α)-Z-DL-2,3-二氨基丙酸N-羧基硫代羰基环内酸酐(简称DAP)进行共聚,得到了系列β-氨基酸聚合物(DAPxBuy)n。抗菌测试表明,制备的(DAPxBuy)n聚合物可通过协同增效,有效逆转白色念珠菌(C. albicans)对伊曲康唑的耐药性,使伊曲康唑的抗真菌最低抑制质量浓度从单药的大于200 μg/mL降低至协同后的3.1 μg/mL,即从无效逆转为高效抗真菌活性。此外,(DAPxBuy)n聚合物在400 μg/mL的高浓度下基本没有造成明显的人血红细胞溶血和细胞毒性。(DAPxBuy)n聚合物能实现高效协同增效和逆转真菌对伊曲康唑的耐药性。

     

  • 图  1  (DAPx Buyn系列β-氨基酸聚合物的合成

    Figure  1.  Synthetic route of (DAPx Buy)n series of β-amino acid polymers

    图  2  系列聚合物的1H-NMR图谱

    Figure  2.  1H-NMR spectra of series of polymers

    图  3  C. albicans (K1菌株)在不同质量浓度药物联合作用下的生长情况

    Figure  3.  Growth of C. albicans (strain K1) incubated with different mass concentrations of polymers and itraconazole

    图  4  系列聚合物的溶血率

    Figure  4.  Hemolysis rates of series of polymers

    图  5  聚合物的细胞毒性

    Figure  5.  Cytotoxicity of polymers

    表  1  聚合物与伊曲康唑的MIC、FICI及相互作用模式

    Table  1.   Interaction modes of polymers and itraconazole and their MIC and FICI values

    PolymerMICalone /(μg·mL−1)MICcombined /(μg·mL−1)FICIEffect
    ItraconazolePolymerItraconazolePolymer
    (DAP0.9Bu0.1)20 >200 3.1 6.3 0.8 0.29 Synergistic
    (DAP0.8Bu0.2)20 >200 3.1 6.3 0.8 0.29 Synergistic
    (DAP0.7Bu0.3)20 >200 6.3 3.1 1.6 0.27 Synergistic
    (DAP0.6Bu0.4)20 >200 6.3 4.7 1.6 0.28 Synergistic
    (DAP0.5Bu0.5)20 >200 12.5 3.1 3.1 0.26 Synergistic
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  • 收稿日期:  2022-04-03
  • 录用日期:  2022-04-27
  • 网络出版日期:  2022-04-29
  • 刊出日期:  2022-12-01

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