| 协同氟康唑抗耐药白念珠菌化合物的设计合成及活性研究 |
| 投稿时间：2016-01-04 修订日期：2016-01-25 点此下载全文 |
| 引用本文：赵晶,李冉,代黎,蔡瞻,张大志,姜远英.协同氟康唑抗耐药白念珠菌化合物的设计合成及活性研究[J].药学实践杂志,2016,34(2):129~134 |
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| 作者 | 单位 | E-mail | | 赵晶 | 福建中医药大学药学院, 福建 福州 350122
第二军医大学药学院, 有机化学教研室, 上海 200433 | | | 李冉 | 第二军医大学药学院, 有机化学教研室, 上海 200433 | | | 代黎 | 第二军医大学药学院, 有机化学教研室, 上海 200433 | | | 蔡瞻 | 第二军医大学药学院, 有机化学教研室, 上海 200433 | | | 张大志 | 福建中医药大学药学院, 福建 福州 350122
第二军医大学药学院, 有机化学教研室, 上海 200433 | zdzhang_yjhx@smmu.edu.cn | | 姜远英 | 第二军医大学药学院, 新药研究中心, 上海 200433 | 13761571578@163.com |
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| 基金项目:国家自然科学基金(21272270) |
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| 中文摘要:目的 基于前期研究的胡椒乙胺和咖啡酸类化合物分别具有协同氟康唑(FCZ)抗耐药真菌的作用,将两类化合物结构片段通过适当的连接子连接,设计合成新型化合物,研究其体外抗耐药真菌活性。方法 以胡椒乙胺为起始原料,与叔丁氧羰基保护的氨基酸缩合,随后脱保护基,再与咖啡酸缩合,形成目标化合物。对4个中间体和9个目标化合物进行体外协同FCZ抗耐药白念珠菌作用评价。结果 9个目标化合物均具有协同FCZ(8.0μg/ml)抗耐药白念珠菌活性,MIC80为0.5~2.0μg/ml;其中, 3b、3f、3g、3i等化合物的MIC80均为0.5μg/ml,与对照化合物7b和5相当。结论 将胡椒乙胺和咖啡酸通过4-哌啶甲酸(3b)、缬氨酸(3g)、亮氨酸(3f)、异亮氨酸(3i)连接,可以获得协同FCZ抗耐药真菌的高活性化合物。 |
| 中文关键词:抗真菌 耐药 协同 合成 白念珠菌 |
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| Design, synthesis and evaluation of the compounds combined with fluconazole against drug resistant Candida albicans |
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| Abstract:Objective 3,4-Methylenedioxyphenethylamine and caffeic acid derivatives have been proven previously in our group to produce activity against drug resistant fungi synergistic with fluconazole(FCZ). The two pharmacophores were coupled by amino acids as linkers in this project in order to design and synthesize the novel compounds and investigate the activity against drug resistant fungi in vitro. Methods 3,4-Methylenedioxyphenethylamine initially reacted with Boc-protected amino acids, following deprotection and coupling reaction with caffeic acid, to get nine title compounds. All title compounds as well as four intermediates were subjected to antifungal activity screening for fluconazole resistant Candida albicans in vitro. Results Nine title compounds showed synergistic antifungal activity for drug resistant Candida albicans with fluconazole at a concentration range of 0.5-2.0μg/ml. Among them, compounds 3b, 3f, 3g and 3i showed the higher activity with the same MIC80 value of 0.5μg/ml, which is comparable to those of the control compounds 7b and 5. Conclusion Linking 3,4-methylenedioxyphenethylamine and caffeic acid with piperidine-4-carboxylic acid(3b), valine(3g), leucine(3f) and isoleucine(3i) led to novel compounds with high synergistic antifungal activity against drug resistant Candida albicans combined with fluconazole. |
| keywords:antifungal drug resistant synergism synthesis Candida albicans |
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