CN108354926B - 一种灯盏乙素及衍生物在抗真菌药物中的应用 - Google Patents
一种灯盏乙素及衍生物在抗真菌药物中的应用 Download PDFInfo
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Abstract
本发明公开了灯盏乙素及衍生物(I)在抗真菌药物中的应用。式中R1为葡萄糖醛酸、R2和R3为氢；R1、R2和R3为氢；R1、R2和R3为乙酰基；R1为正己基、正十二基、正十八基、油烯基，R2为氢或乙酰基，R3为乙酰基。灯盏乙素及衍生物(I)联合氟康唑对白色念珠菌耐药株有很好的抗真菌活性，具有应用前景。
Description
技术领域
本发明属于医药技术领域，具体涉及灯盏乙素及其衍生物(I)在抗真菌药物中的应用。
背景技术
随着抗生素、糖皮质激素、器官移植和导管插管等药品和技术的广泛应用和以及艾滋病等免疫缺陷病患者人数的上升，真菌感染发病率不断提高。同时，真菌的耐药性严重影响药物疗效，危害患者的生命安全，开发新的抗真菌药物非常重要。
白色念珠菌是常见的条件致病菌，在免疫力较低的器官移植者、艾滋病患者和长期进行肿瘤化疗、使用糖皮质激素或大量广谱抗菌药物的患者中容易引发感染，引发念珠菌菌血症、鹅口疮、念珠菌性阴道炎等疾病。其治疗期限较长，有效药物品种有限。由于患者的用药依从性较差，导致耐药菌株日益增多。
灯盏细辛是云南省特有的天然药物之一，为菊科紫菀族飞蓬属植物短葶飞蓬[Erigeron breviscapus (Vant.) Hand.-mazz]，其制剂广泛安全的应用于临床。灯盏乙素是灯盏细辛的主要有效成分，又名野黄芩苷，体内的主要活性代谢产物为灯盏乙素苷元。研究发现，灯盏乙素及其苷元具有抗氧化等作用。而在抗真菌方面还尚无人研究。我们在前期合成了一系列灯盏乙素衍生物，我们将衍生物与灯盏乙素进行抗真菌活性研究，意外地发现灯盏乙素及其衍生物联合氟康唑对白色念球菌特别是耐药株具有较好的抗真菌活性。
发明内容
本发明的目的在于提供灯盏乙素及其衍生物(I)在抗真菌药物中的应用。
本发明的目的是这样实现的：
一种如其结构通式如(I)所示的灯盏乙素及其衍生物在抗真菌药物中的应用，式中R1为葡萄糖醛酸、R2和R3为氢；R1、R2和R3为氢；R1、R2和R3为乙酰基；R1为正己基、正十二基、正十八基、油烯基，R2为氢或乙酰基，R3为乙酰基。
真菌为念球菌属。
真菌为白色念球菌。
真菌为白色念球菌标准株和白色念球菌耐药株。
本发明优点：
本发明提供的化合物联合氟康唑对白色念珠菌耐药株具有抗真菌活性。
具体实施方式
下面对本发明作进一步的说明，但不以任何方式对本发明加以限制，基于本发明所作的任何变换，均属于本发明的保护范围。
一种如其结构通式如(I)所示的灯盏乙素及其衍生物在抗真菌药物中的应用，式中R1为葡萄糖醛酸、R2和R3为氢；R1、R2和R3为氢；R1、R2和R3为乙酰基；R1为正己基、正十二基、正十八基、油烯基，R2为氢或乙酰基，R3为乙酰基。
真菌为念球菌属。
真菌为白色念球菌。
真菌为白色念球菌标准株和白色念球菌耐药株。
实施例1：
对白色念珠菌标准株和耐药株的抑菌试验
取96孔培养板，阳性药物氟康唑稀释成初浓度为200ug/ml，待测样品稀释成初浓度为200μmol/L,阳性药物和待测样品联合用药，两个浓度翻倍，体积减半；然后进行5倍倍比稀释，6个浓度梯度，每个浓度梯度3个重复孔。各孔加入真菌菌悬液，标准株和耐药株的浓度均为1× 105 CFU/mL，37 °C分别培养24 h。酶标仪测定625 nm下的OD值。实验同时设置培养基空白对照、菌液对照以及氟康唑阳性药物对照。
联合用药试验
取96孔培养板，待测样品和阳性对照药物1：1体积加入孔中，混匀后进行5倍倍比稀释，6个浓度梯度，每个浓度梯度3个重复孔。各孔加入白色念珠菌菌悬液，标准株和耐药株的浓度均为1× 105 CFU/mL。37 °C培养24 h，酶标仪测定625 nm下的OD值。实验同时设置培养基空白对照、菌液对照。
根据实验结果，按Reed＆Muench法计算出样品抑制真菌的50％有效浓度(EC50)。
真菌活性抑制率（%）= （1 – 样品OD值 / 实验对照孔OD值）× 100%
样品对白色念珠菌标准株和耐药株抑菌作用的实验数据
Claims (1)
1.一种灯盏乙素及其衍生物和氟康唑的药物组合物在制备抗白色念珠菌耐药株药物中的应用，其特征在于所述灯盏乙素及其衍生物如结构通式（I）所示：
其中：R1、R2、R3为氢，或者R1、R2、R3为乙酰基，或者R1为正己基、R2和R3为乙酰基，或者R1为正己基、R2为氢、R3为乙酰基，或者R1为油烯基、R2为氢、R3为乙酰基。
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| In vitro antifungal activity of the aqueous extract of Scutellaria baicalensis Georgi root against Candida albicans;Kin SingWong;《International Journal of Antimicrobial Agents》;20091231;第284-285页 * |
| 灯盏花乙素苷元的微生物限度检查方法验证;赵加强等;《中国民族民间医药》;20150211;赵加强等 * |
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