CN102234232B - 江西烯酮酯及其应用 - Google Patents
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Abstract
本发明公开了一种江西烯酮酯，它的结构式为（I）。江西烯酮酯具有显著的抗肿瘤效应。10μM浓度的江西烯酮酯对肺癌A549和胃癌SGC-7901细胞的生长抑制率分别高达92.7±2.6%和96.5±3.5%。抑制效果相当于83.3μM浓度的一线药物顺铂的药效。
Description
技术领域
本发明涉及一种化合物及其应用，尤其是一种江西烯酮酯及其应用。
背景技术
癌症是危害人类健康最严重的疾病之一。据美国癌症学会最新统计表明，2007年全球1200万新发病例，死亡760万，且以每年数十万的态势高速增长，预计2050年新发病例将达2700万，死亡1750万（参见American Cancer Society. Cancer Facts & Figures 2007. Atlanta: 2007.），癌症已成为21世纪人类健康的头号杀手。化疗仍然是当前治疗癌症的主要手段之一。因此，创制新型高效抗癌药物显得尤为迫切和重要。上世纪40年代至今，73%的抗肿瘤化疗药物是来源动植物、微生物和海洋生物等天然药源。因此，从天然药源中筛选抗肿瘤高效药物国际医药界关注的热点之一。
发明内容
本发明的目的是：提供一种江西烯酮酯及其应用，它是一种新的化合物，它能用于制备治疗或预防癌症的药物。
本发明是这样实现的：江西烯酮酯，它是从江西虫草（Cordyceps jiangxiensis）的发酵菌体中提取获得的，经现代波谱技术确定了其化学结构为
江西烯酮酯在治疗或预防癌症药物中的应用，将江西烯酮酯用于制备治疗或预防癌症的药物。
江西烯酮酯抑制肿瘤细胞增殖活性检测：
用于研究的肿瘤细胞株A549和SGC-7901均购自于中国科学院上海生命科学研究院细胞资源中心；所用培养基为常规RPMI1640培养基，并含10～15%胎牛血清。
实验过程如下：对数生长期细胞制备细胞悬液，加入96孔培养板，每孔100μL，细胞数5.0×103/孔，然后置于5%CO2，95%湿度的孵箱37°C培养24小时，再加入一定浓度的待测药物100μL，继续培养48小时。抗肿瘤细胞毒效应实验采用国际通用的SRB法检测，即取出培养板后，每孔加入预冷的50%三氯醋酸50μL，在4°C下固定1小时，去除液体后用超纯水洗5次，甩干后自然晾干，然后加入0.4%SRB的醋酸溶液 100μL，室温放置10～30min后，用1%醋酸水溶液清洗5次，除去未结合的游离SRB 、晾干。再按每孔150μL非缓冲Tris碱液（10mmol/L，pH10.5）溶解蛋白结合的SRB。酶标仪检测波长490nm处的吸光度值。每个药物浓度设置4个复孔，设置本底调零孔、阴性空白对照、DMSO溶剂对照和25μg/mL（83.3μM）的顺铂（Cisplatin）阳性对照。
注：计算细胞抑制率IR%=(1-OD阴性对照/OD试样)×100。
实验结果见图1
根据图1的内容可以得知，江西烯酮酯具有显著的抗肿瘤效应。10μM浓度的江西烯酮酯对肺癌A549和胃癌SGC-7901细胞的生长抑制率分别高达92.7±2.6%和96.5±3.5%。抑制效果相当于83.3μM浓度的一线药物顺铂的药效。
江西烯酮酯（jiangxienone）为无色针状晶体，熔点147～149oC，分子式C28H40O4。其结构是基于其质谱和核磁共振等波谱数据以及计算而确定的。
红外光谱数据：IR (KBr), 3444cm-1, 2958 cm-1, 2924 cm-1, 2851cm-1, 1736 cm-1, 1702 cm-1, 1680cm-1, 1659cm-1。
紫外光谱UV在约250nm左右有吸收特征峰。
质谱数据：HRESIMS: calcd for C28H40NaO4: m/z 463.2824, found 463.2804。
有关核磁共振数据见表1，碳氢异核多间相关见图2。
表1：江西烯酮酯的核磁共振数据表
附图说明
附图1为江西烯酮酯对肿瘤细胞生长的抑制作用图；
附图1为江西烯酮酯的碳氢异核多间相关图。
具体实施方式
本发明的实施例1：将江西虫草（Cordyceps jiangxiensis）的菌丝体用蒸馏水洗3次后55～60oC干燥至恒重；干燥的菌丝体经粉碎后获得菌丝粉约3000g，用有机溶剂反复提取，获得提取物，萃取物用温水混悬后用石油醚反复萃取，进行脱脂处理；石油醚萃取后的残留液用三氯甲烷反复获得三氯甲烷有效萃取部位约81g；对三氯甲烷萃取部位进行硅胶柱层析，再用石油醚-乙酸乙酯（PE-EtAc）进行梯度洗脱，在PE-EtAc（5:1）洗脱段获得一组分约18g；该组分进一步进行硅胶柱层析后，用石油醚-丙酮（PE-A）进行梯度洗脱，在PE-A（15:1）洗脱段获得江西烯酮酯纯品35mg。
该方法分离出的化合物江西烯酮酯化学结构式为：
将江西烯酮酯纯品的晶体与赋形剂（淀粉、玉米浆、硬脂酸镁）分别以质量比1：1、1：2及1：3的比例，按常规粒片剂方法制成粒压片。
本发明的实施例2：将江西烯酮酯纯品的晶体与填料辅剂（淀粉、硬脂酸镁）按常规硬胶囊制剂方法制成胶囊。
本发明的实施例3：将江西烯酮酯纯品溶解于2mL丙二醇中，再通过微孔滤膜过滤，所得溶液在无菌条件下装入安瓿瓶中。
Claims (2)
1.江西烯酮酯，其特征在于：它的结构式为
2.江西烯酮酯在治疗或预防癌症药物中的应用，其特征在于：将江西烯酮酯用于制备治疗或预防癌症的药物。
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