| 组蛋白去乙酰化酶抑制剂Rocilinostat的抗真菌活性研究 |
| 投稿时间：2021-03-09 修订日期：2021-05-31 点此下载全文 |
| 引用本文：朱天宝,涂杰,盛春泉,徐德锋,刘娜.组蛋白去乙酰化酶抑制剂Rocilinostat的抗真菌活性研究[J].药学实践杂志,2022,40(1):44~47,65 |
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| 基金项目:国家自然科学基金面上项目（81973175） |
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| 中文摘要:目的 探索组蛋白去乙酰化酶（HDAC）抑制剂与唑类药物联用对唑类耐药念珠菌的体外协同的抗真菌活性。方法 根据棋盘稀释法，测试HDAC抑制剂和唑类药物联用对临床耐药株的协同抗真菌活性，通过时间-生长曲线实验和细胞毒性实验对化合物Rocilinostat的抑菌效果、毒性进行考察。结果 化合物Rocilinostat与唑类药物联用对多种耐药白念珠菌和光滑念珠菌均表现出优秀的协同抗真菌活性，并且其在高浓度下与氟康唑联用表现出抑菌效果。此外，化合物Rocilinostat对正常细胞表现出低毒性，且对白念珠菌HDAC具有强烈的抑制活性，优于对照药伏立诺他。结论 化合物Rocilinostat作为真菌HDAC抑制剂，具有优秀的体外协同抗真菌活性，且对真菌细胞具有较好的选择性作用。 |
| 中文关键词:组蛋白去乙酰化酶抑制剂 体外协同抗真菌活性 耐药 白念珠菌 |
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| Antifungal activity study on HDAC inhibitor Rocilinostat |
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| Abstract:Objective To evaluate the in vitro synergistic antifungal activity of HDAC inhibitors in combination with azole drugs against azoles-resistant Candida strains.Methods The checkerboard microdilution method was used to evaluate the antifungal activity of the HDAC inhibitors in combination with azole drugs against clinically drug-resistant strains. The fungistatic activity and toxicity of Rocilinostat was determined through time-growth curve assay and cytotoxicity assay.Results The compound Rocilinostat combined with azole drugs showed excellent synergistic antifungal activity against a variety of azoles-resistant Candida albicans and Candida glabrata. The combination of high concentration Rocilinostat with FLC exhibited fungistatic effects. Very low toxicity was detected with Rocilinostat towards normal cells. Rocilinostat showed better HDAC inhibitory activity than SAHA.Conclusion As a fungi HDAC inhibitor, Rocilinostat has excellent in vitro synergistic antifungal activity and no severe toxicity to normal human cells. |
| keywords:HDAC inhibitors in vitro synergistic antifungal activity resistant Candida albicans |
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