Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Mar Drugs. 2018 Sep 5;16(9):315. doi: 10.3390/md16090315.
Hydroxypropyltrimethyl ammonium chitosan halogenated acetates were successfully synthesized from six different haloacetic acids and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) with high substitution degree, which are hydroxypropyltrimethyl ammonium chitosan bromacetate (HACBA), hydroxypropyltrimethyl ammonium chitosan chloroacetate (HACCA), hydroxypropyltrimethyl ammonium chitosan dichloroacetate (HACDCA), hydroxypropyltrimethyl ammonium chitosan trichloroacetate (HACTCA), hydroxypropyltrimethyl ammonium chitosan difluoroacetate (HACDFA), and hydroxypropyltrimethyl ammonium chitosan trifluoroacetate (HACTFA). These chitosan derivatives were synthesized by two steps: first, the hydroxypropyltrimethyl ammonium chloride chitosan was synthesized by chitosan and 3-chloro-2-hydroxypropyltrimethyl ammonium chloride. Then, hydroxypropyltrimethyl ammonium chitosan halogenated acetates were synthesized via ion exchange. The structures of chitosan derivatives were characterized by Fourier transform infrared spectroscopy (FTIR), ¹H Nuclear magnetic resonance spectrometer (¹H NMR), C Nuclear magnetic resonance spectrometer (C NMR), and elemental analysis. Their antifungal activities against , , , and were investigated by hypha measurement in vitro. The results revealed that hydroxypropyltrimethyl ammonium chitosan halogenated acetates had better antifungal activities than chitosan and HACC. In particular, the inhibitory activity decreased in the order: HACTFA > HACDFA > HACTCA > HACDCA > HACCA > HACBA > HACC > chitosan, which was consistent with the electron-withdrawing property of different halogenated acetates. This experiment provides a potential idea for the preparation of new antifungal drugs by chitosan.
羟丙基三甲基氯化铵壳聚糖卤代乙酸酯是由六种不同的卤代乙酸和高取代度的羟丙基三甲基氯化铵壳聚糖（HACC）成功合成的，它们分别是羟丙基三甲基氯化铵溴乙酸酯（HACBA）、羟丙基三甲基氯化铵氯乙酸酯（HACCA）、羟丙基三甲基氯化铵二氯乙酸酯（HACDCA）、羟丙基三甲基氯化铵三氯乙酸酯（HACTCA）、羟丙基三甲基氯化铵二氟乙酸酯（HACDFA）和羟丙基三甲基氯化铵三氟乙酸酯（HACTFA）。这些壳聚糖衍生物是通过两步法合成的：首先，壳聚糖与 3-氯-2-羟丙基三甲基氯化铵反应合成羟丙基三甲基氯化铵壳聚糖；然后，通过离子交换法合成羟丙基三甲基氯化铵卤代乙酸酯。通过傅里叶变换红外光谱（FTIR）、1H 核磁共振谱（1H NMR）、C 核磁共振谱（C NMR）和元素分析对壳聚糖衍生物的结构进行了表征。通过体外菌丝测量法研究了它们对 、 、 、 和 的抗真菌活性。结果表明，羟丙基三甲基氯化铵壳聚糖卤代乙酸酯比壳聚糖和 HACC 具有更好的抗真菌活性。特别是，抑制活性按以下顺序降低：HACTFA>HACDFA>HACTCA>HACDCA>HACCA>HACBA>HACC>壳聚糖，这与不同卤代乙酸酯的吸电子性质一致。该实验为壳聚糖制备新型抗真菌药物提供了一个潜在的思路。
