文献类型：期刊文献

中文题名：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

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

作者：马凯茜[1];张东辉[1];施超[1];顾佳蔚[1];刘润辉[1]

机构：[1]华东理工大学生物反应器工程国家重点实验室,超细材料制备与应用教育部重点实验室,教育部医用生物材料工程研究中心,材料科学与工程学院,上海200237

年份：2022

卷号：35

期号：6

起止页码：532

中文期刊名：功能高分子学报

外文期刊名：Journal of Functional Polymers

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(22075078,21861162010);上海市优秀学术带头人(20XD1421400)。

语种：中文

中文关键词：β-氨基酸聚合物;伊曲康唑;协同增效;逆转真菌耐药性;抗真菌

外文关键词：β-amino acid polymer;itraconazole;synergistic effect;reversing fungal resistance;antifungal

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(DAP_(x)Bu_(y))_(n)。抗菌测试表明,制备的(DAP_(x)Bu_(y))_(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200μg/mL降低至协同后的3.1μg/mL,即从无效逆转为高效抗真菌活性。此外,(DAP_(x)Bu_(y))_(n)聚合物在400μg/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。(DAP_(x)Bu_(y))_(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。
In this study,a series of β-amino acid polymers which have synergistic antifungal activity with itraconazole were designed and synthesized.The random copolymers (DAP_(x)Bu_(y))_(n) were obtained by ring-opening polymerization of β-amino acid N-thiocarboxyanhydrides(β-NTA)under room temperature using 4-tert-Butylbenzylamine(tBuBz-NH_(2))as an initiator,with DL-β-norleucine N-thiocarboxyanhydrides as hydrophobic monomer and N(α)-Z-DL-2,3-diaminopropionic acid Nthiocarboxyanhydrides as cationic monomer.The effect of (DAP_(x)Bu_(y))_(n) combined with itraconazole on C.albicans was evaluated by checkerboard antifungal test.The test showed that (DAP_(x)Bu_(y))_(n) copolymers could effectively reverse itraconazole resistance in C.albicans through synergistic effect,while the minimum inhibitory concentration(MIC)of antifungal of itraconazole was reduced from more than 200μg/mL to 3.1μg/mL after exposure to(DAP_(x)Bu_(y))_(n),indicating that the antifungal activity of itraconazole reversed from ineffective to highly effective.In addition,most of (DAP_(x)Bu_(y))_(n) copolymers did not cause significant hemolysis of human red blood cells and fibroblasts toxicity at a high concentration of 400μg/mL.Our studies demonstrate that the(DAP_(x)Bu_(y))_(n) copolymers can achieve efficient synergistic effect with itraconazole and reverse itraconazole resistance in C.albicans,showing broad potential in the treatment of fungal infections.